combining old and new: sensitising drugs and other vaccines to augment efficacy of dendritic cell...
TRANSCRIPT
Combining Old and New Sensitising Drugs and Other Vaccines ToAugment Efficacy of Dendritic Cell Immunotherapy
Cost-effective candidates
Levamisole BCG Imiquimod Mifamurtide amp Dendritic Vax
Nature 2015 Mar 19519(7543)366-9 doi
101038nature14320 Epub 2015 Mar 11
Nature 2015 Mar 19519(7543)366-9 doi
101038nature14320 Epub 2015 Mar 11
Experiments showed that CCL3 upregulation in the skin was dependent on the induction of the Td recall response and was significantly reduced by CD4+ T cell depletion
bull Toll-like receptors (TLRs) are a class of proteins that play a key role in the innate immune system They are single membrane-spanning non-catalytic receptors usually expressed in sentinel cells such as macrophages and dendritic cells that recognize structurally conserved molecules derived from microbes Once these microbes have breached physical barriers such as the skin or intestinal tract mucosa they are recognized by TLRs which activate immune cell responses The TLRs include TLR1 TLR2 TLR3 TLR4 TLR5 TLR6 TLR7 TLR8 TLR9 TLR10TLR11 TLR12 and TLR13 though the latter two are not found in humans
Levamisole marketed under the trade name Ergamisol is a medication used to treat parasitic worm infections It has also been studied as a method to stimulate the immune system as part of the treatment of cancer Most current commercial preparations are intended for veterinary use as a dewormer in cattle pigs and sheep
After being pulled from the market in the US and Canada in 1999 and 2003 respectively levamisole has been tested in combination with fluorouracil to treat colon cancer Evidence from clinical trials support its addition to fluorouracil therapy to benefit patients with colon cancer
One of the more serious side effects of Levamisole is agranulocytosis or the depletion of the white blood cells In particular neutrophils appear to be affected the most This occurs in 008-5 of the studied populations
There have also been reports of levamisole induced necrosis syndrome in which erythematous painful papules can appear almost anywhere on skin
Levamisole was evaluated as
an immune stimulant in a
randomized controlled study
of patients with anaplastic
gliomas who had undergone
surgical resection and who
were also treated with
radiotherapy and BCNU chemotherapy
Studies utilizing the avian sarcoma virus-induced glioma in rats also showed no
improvement in survival with levamisole stimulation as the only immune agent but
the combination of active immunization and adjuvant stimulation with bacillus
Calmette-Guerin plus levamisole was found to be therapeutically effective in this model and will be used in future pilot studies of active immunization in patients
Levamisole is a synthetic phenylimidazolthiazole that was first introduced in 1966 as an anti-helmintic agent
Current studies have been focused upon its effect on immune response and on cancer treatment
We examined the molecular mechanisms of levamisole in the activation and maturation of human
monocyte-derived dendritic cells (DC) and human T cells
Treatment of DC with levamisole increased the presentation of CD80 CD86 CD83 and human
leucocyte antigen D-related (HLA-DR) molecules on the cell membrane as well as the production of
interleukin-12 p40 and IL-10
Levamisole-treated human DC also enhanced T cell activation towards type 1 T helper immune
response by inducing interferon-γ secretion Neutralization with antibodies against Toll-like receptor
(TLR)-2 inhibited levamisole-induced production of IL-12 p40 and IL-10 suggesting a vital role for TLR-2
in signalling DC upon incubation with levamisole
In this study we showed that BALBc bone marrow-derived DC stimulated with LMS resulted in enhanced cell-
surface expression of CD80 CD86 CD40 and MHC class II as well as enhanced production of IL-12p70 TNF-α
and IL-1β Interestingly the LMS activated DCs were able to stimulate CD4(+) T cell proliferation and facilitated
Th1 differentiation by increasing the secretion of IFN-γ in an allogeneic mixed leukocyte reaction Furthermore to
confirm the in vitro data we investigated the effect of LMS on antigen-specific antibody and cytokine
production in BALBc mice Immunization with LMS plus OVA showed that anti-OVA IgG2a and IFN-γ were
increased significantly compared with OVA alone in BALBc mice
bull Aliment Pharmacol Ther 2010 Sep32(6)756-62 Meta-analysis levamisole improves the immune response to hepatitisBvaccine in dialysis patients
bull Fabrizi F1 Dixit V Messa P Martin P
bull We identified four studies involving 328 unique patients on regular dialysis Only prospective randomized clinical trials (RCTs) were included
bull Pooling of study results showed a significant increase in response rates among study (levamisole plus HBV vaccine) vs control (HBV vaccine alone) patients the pooled Odds Ratio was 2432 (95 Confidence Intervals 134 4403) P = 0002
bull Nephrology (Carlton) 2014 Jan19(1)27-31 Effectof levamisole supplementation on tetanus vaccination response rates in haemodialysis patients a randomized double-blind placebo-controlledtrial Fallahzadeh MK1 Sajjadi S Singh N Khajeh M Sagheb MM
bull At 6 months 11 out of 15 (73) patients in the levamisole group as compared with four out of 16 (25) patients in the placebo group still had protective anti-tetanus IgG levels (relative riskthinsp=thinsp293 95 CIthinsp=thinsp119 723)
bull Supplementation of Td vaccination with levamisole may enhance seroconversion against tetanus in haemodialysis patients
BCG is an attenuated (nonvirulent) form of Mycobacterium bovis cultured in 1921 by Albert Calmette and Camille Guerin at the Pasteur Institute in Lille France In the late 1920rsquos autopsy studies performed at Johns Hopkins Hospital in Baltimore Maryland showed a lower frequency of cancer in patients with tuberculosis
Attempts were made to use BCG against a variety of human cancer tumors with only limited success It wasnrsquot until the 1970rsquos however that a Canadian urologist Dr Alvaro Morales began his groundbreaking work on the use of intravesical BCG for the treatment of superficial bladder cancer Over 30 years later BCG continues to be used worldwide for the treatment of high grade noninvasive bladder cancer
Mycobacterium bovis (TEM)
We investigated whether three mycobacterial preparations currently used in the clinic (BCG and heat-killed Mycobacterium vaccae and Mycobacterium obuense) can stimulate anti-tumoureffector responses in human γδ T-cells Results show that γδ T-cells are activated by these mycobacterial preparations as indicated by upregulation of activation marker expression and proliferation
Activated γδ T-cells display enhanced effector responses as shown by upregulated granzyme B expression production of the T(H)1 cytokines IFN-γ and TNF-α and enhanced degranulation in response to susceptible and resistant tumour cells
A type of metastasis in which skin cancer spreads through a lymph vessel and begins to grow more than 2 centimeters away from the primary tumor but before it reaches the nearest lymph node
For the small uncontrolled study twenty (20) patients in advanced stages with limited life expectancy were recruited in a 2-year period Patients were classified into two groups according to the treatment to be employed Group 1 included 6 patients who refused to be treated with standard treatments and received only immunotherapy Group 2 included 14 patients treated with both immunotherapy and chemotherapyradiotherapy (CTRT) The vaccination procedure 3 intradermal doses of 05 ml each with intervals of 6 weeks between each dose Tumor fragments (about 1 g) from patients were kept in sterile PBS at minus80 degC until use For each dose about 03ndash04 g of tumor tissue were macerated in 06 ml sterile PBS
At the moment of vaccination the soluble fraction of the homogenate was mixed with formaldehyde 36 at a final concentration of 002 and 06 ml of BCG suspension 015
The survival rate upon a 5-year period was plotted for the immunotherapy only (IT) group and the combined treated (CTRTIT) group as well as for the overall survival across all subjects The calculated 5-year survival is indicated for each plot
However γδ T cells are peculiar in that they do not seem to require antigen processing and major-histocompatibility-complex (MHC) presentation of peptide epitopes although some recognize MHC class Ib molecules Furthermore γδ T cells are believed to have a prominent role in recognition of lipid antigens
Imiquimod
Imiquimod (INN) is a prescription medication that acts as an immune response modifier and is used to treat genital warts superficial basal cell carcinoma and actinic keratosis Imiquimod signals to the innate arm of the immune system through the toll-like receptor 7 (TLR7)
Plasmacytoid dendritic cells (pDCs) are innate immune cells that circulate in the blood and are found in peripheral lymphoid organs They constitute lt 04 of peripheral blood mononuclear cells (PBMC) In humans these cells express the surface markers CD123 BDCA-2(CD303) and BDCA-4 (CD304) but do not express high levels of CD11c or CD14 which distinguishes them from conventional dendritic cells or monocytes respectively
TNF-related apoptosis-inducing ligand (TRAIL) is aprotein functioning as a ligand that induces the process of cell death called apoptosis TRAIL is a cytokine that is produced and secreted by most normal tissue cells It causes apoptosis primarily in tumor cells by binding to certain death receptors TRAIL has also been designated CD253 (cluster of differentiation 253)
Melanoma in situ ndash Lentigo malignaImiquimod Treatment
Mifamurtide (Mepactreg Takeda) is a drug against osteosarcoma
mainly affecting children and young adults which is lethal in about a third of cases The drug was approved in Europe in March 2009
In a phase-III clinical trial in about 800 newly diagnosed osteosarcoma patients
mifamurtide was combined with the chemotherapeutic agents doxorubicin and
methotrexate with or without cisplatin and ifosfamide The mortality could be lowered
by 30 versus chemotherapy plus placebo Six years after the treatment 78 of patients were alive Drugs in RampD 9 (2) 131ndash5 2008
Looking to the past may help planning for thefuture
Nature 2015 Mar 19519(7543)366-9 doi
101038nature14320 Epub 2015 Mar 11
Nature 2015 Mar 19519(7543)366-9 doi
101038nature14320 Epub 2015 Mar 11
Experiments showed that CCL3 upregulation in the skin was dependent on the induction of the Td recall response and was significantly reduced by CD4+ T cell depletion
bull Toll-like receptors (TLRs) are a class of proteins that play a key role in the innate immune system They are single membrane-spanning non-catalytic receptors usually expressed in sentinel cells such as macrophages and dendritic cells that recognize structurally conserved molecules derived from microbes Once these microbes have breached physical barriers such as the skin or intestinal tract mucosa they are recognized by TLRs which activate immune cell responses The TLRs include TLR1 TLR2 TLR3 TLR4 TLR5 TLR6 TLR7 TLR8 TLR9 TLR10TLR11 TLR12 and TLR13 though the latter two are not found in humans
Levamisole marketed under the trade name Ergamisol is a medication used to treat parasitic worm infections It has also been studied as a method to stimulate the immune system as part of the treatment of cancer Most current commercial preparations are intended for veterinary use as a dewormer in cattle pigs and sheep
After being pulled from the market in the US and Canada in 1999 and 2003 respectively levamisole has been tested in combination with fluorouracil to treat colon cancer Evidence from clinical trials support its addition to fluorouracil therapy to benefit patients with colon cancer
One of the more serious side effects of Levamisole is agranulocytosis or the depletion of the white blood cells In particular neutrophils appear to be affected the most This occurs in 008-5 of the studied populations
There have also been reports of levamisole induced necrosis syndrome in which erythematous painful papules can appear almost anywhere on skin
Levamisole was evaluated as
an immune stimulant in a
randomized controlled study
of patients with anaplastic
gliomas who had undergone
surgical resection and who
were also treated with
radiotherapy and BCNU chemotherapy
Studies utilizing the avian sarcoma virus-induced glioma in rats also showed no
improvement in survival with levamisole stimulation as the only immune agent but
the combination of active immunization and adjuvant stimulation with bacillus
Calmette-Guerin plus levamisole was found to be therapeutically effective in this model and will be used in future pilot studies of active immunization in patients
Levamisole is a synthetic phenylimidazolthiazole that was first introduced in 1966 as an anti-helmintic agent
Current studies have been focused upon its effect on immune response and on cancer treatment
We examined the molecular mechanisms of levamisole in the activation and maturation of human
monocyte-derived dendritic cells (DC) and human T cells
Treatment of DC with levamisole increased the presentation of CD80 CD86 CD83 and human
leucocyte antigen D-related (HLA-DR) molecules on the cell membrane as well as the production of
interleukin-12 p40 and IL-10
Levamisole-treated human DC also enhanced T cell activation towards type 1 T helper immune
response by inducing interferon-γ secretion Neutralization with antibodies against Toll-like receptor
(TLR)-2 inhibited levamisole-induced production of IL-12 p40 and IL-10 suggesting a vital role for TLR-2
in signalling DC upon incubation with levamisole
In this study we showed that BALBc bone marrow-derived DC stimulated with LMS resulted in enhanced cell-
surface expression of CD80 CD86 CD40 and MHC class II as well as enhanced production of IL-12p70 TNF-α
and IL-1β Interestingly the LMS activated DCs were able to stimulate CD4(+) T cell proliferation and facilitated
Th1 differentiation by increasing the secretion of IFN-γ in an allogeneic mixed leukocyte reaction Furthermore to
confirm the in vitro data we investigated the effect of LMS on antigen-specific antibody and cytokine
production in BALBc mice Immunization with LMS plus OVA showed that anti-OVA IgG2a and IFN-γ were
increased significantly compared with OVA alone in BALBc mice
bull Aliment Pharmacol Ther 2010 Sep32(6)756-62 Meta-analysis levamisole improves the immune response to hepatitisBvaccine in dialysis patients
bull Fabrizi F1 Dixit V Messa P Martin P
bull We identified four studies involving 328 unique patients on regular dialysis Only prospective randomized clinical trials (RCTs) were included
bull Pooling of study results showed a significant increase in response rates among study (levamisole plus HBV vaccine) vs control (HBV vaccine alone) patients the pooled Odds Ratio was 2432 (95 Confidence Intervals 134 4403) P = 0002
bull Nephrology (Carlton) 2014 Jan19(1)27-31 Effectof levamisole supplementation on tetanus vaccination response rates in haemodialysis patients a randomized double-blind placebo-controlledtrial Fallahzadeh MK1 Sajjadi S Singh N Khajeh M Sagheb MM
bull At 6 months 11 out of 15 (73) patients in the levamisole group as compared with four out of 16 (25) patients in the placebo group still had protective anti-tetanus IgG levels (relative riskthinsp=thinsp293 95 CIthinsp=thinsp119 723)
bull Supplementation of Td vaccination with levamisole may enhance seroconversion against tetanus in haemodialysis patients
BCG is an attenuated (nonvirulent) form of Mycobacterium bovis cultured in 1921 by Albert Calmette and Camille Guerin at the Pasteur Institute in Lille France In the late 1920rsquos autopsy studies performed at Johns Hopkins Hospital in Baltimore Maryland showed a lower frequency of cancer in patients with tuberculosis
Attempts were made to use BCG against a variety of human cancer tumors with only limited success It wasnrsquot until the 1970rsquos however that a Canadian urologist Dr Alvaro Morales began his groundbreaking work on the use of intravesical BCG for the treatment of superficial bladder cancer Over 30 years later BCG continues to be used worldwide for the treatment of high grade noninvasive bladder cancer
Mycobacterium bovis (TEM)
We investigated whether three mycobacterial preparations currently used in the clinic (BCG and heat-killed Mycobacterium vaccae and Mycobacterium obuense) can stimulate anti-tumoureffector responses in human γδ T-cells Results show that γδ T-cells are activated by these mycobacterial preparations as indicated by upregulation of activation marker expression and proliferation
Activated γδ T-cells display enhanced effector responses as shown by upregulated granzyme B expression production of the T(H)1 cytokines IFN-γ and TNF-α and enhanced degranulation in response to susceptible and resistant tumour cells
A type of metastasis in which skin cancer spreads through a lymph vessel and begins to grow more than 2 centimeters away from the primary tumor but before it reaches the nearest lymph node
For the small uncontrolled study twenty (20) patients in advanced stages with limited life expectancy were recruited in a 2-year period Patients were classified into two groups according to the treatment to be employed Group 1 included 6 patients who refused to be treated with standard treatments and received only immunotherapy Group 2 included 14 patients treated with both immunotherapy and chemotherapyradiotherapy (CTRT) The vaccination procedure 3 intradermal doses of 05 ml each with intervals of 6 weeks between each dose Tumor fragments (about 1 g) from patients were kept in sterile PBS at minus80 degC until use For each dose about 03ndash04 g of tumor tissue were macerated in 06 ml sterile PBS
At the moment of vaccination the soluble fraction of the homogenate was mixed with formaldehyde 36 at a final concentration of 002 and 06 ml of BCG suspension 015
The survival rate upon a 5-year period was plotted for the immunotherapy only (IT) group and the combined treated (CTRTIT) group as well as for the overall survival across all subjects The calculated 5-year survival is indicated for each plot
However γδ T cells are peculiar in that they do not seem to require antigen processing and major-histocompatibility-complex (MHC) presentation of peptide epitopes although some recognize MHC class Ib molecules Furthermore γδ T cells are believed to have a prominent role in recognition of lipid antigens
Imiquimod
Imiquimod (INN) is a prescription medication that acts as an immune response modifier and is used to treat genital warts superficial basal cell carcinoma and actinic keratosis Imiquimod signals to the innate arm of the immune system through the toll-like receptor 7 (TLR7)
Plasmacytoid dendritic cells (pDCs) are innate immune cells that circulate in the blood and are found in peripheral lymphoid organs They constitute lt 04 of peripheral blood mononuclear cells (PBMC) In humans these cells express the surface markers CD123 BDCA-2(CD303) and BDCA-4 (CD304) but do not express high levels of CD11c or CD14 which distinguishes them from conventional dendritic cells or monocytes respectively
TNF-related apoptosis-inducing ligand (TRAIL) is aprotein functioning as a ligand that induces the process of cell death called apoptosis TRAIL is a cytokine that is produced and secreted by most normal tissue cells It causes apoptosis primarily in tumor cells by binding to certain death receptors TRAIL has also been designated CD253 (cluster of differentiation 253)
Melanoma in situ ndash Lentigo malignaImiquimod Treatment
Mifamurtide (Mepactreg Takeda) is a drug against osteosarcoma
mainly affecting children and young adults which is lethal in about a third of cases The drug was approved in Europe in March 2009
In a phase-III clinical trial in about 800 newly diagnosed osteosarcoma patients
mifamurtide was combined with the chemotherapeutic agents doxorubicin and
methotrexate with or without cisplatin and ifosfamide The mortality could be lowered
by 30 versus chemotherapy plus placebo Six years after the treatment 78 of patients were alive Drugs in RampD 9 (2) 131ndash5 2008
Looking to the past may help planning for thefuture
Nature 2015 Mar 19519(7543)366-9 doi
101038nature14320 Epub 2015 Mar 11
Experiments showed that CCL3 upregulation in the skin was dependent on the induction of the Td recall response and was significantly reduced by CD4+ T cell depletion
bull Toll-like receptors (TLRs) are a class of proteins that play a key role in the innate immune system They are single membrane-spanning non-catalytic receptors usually expressed in sentinel cells such as macrophages and dendritic cells that recognize structurally conserved molecules derived from microbes Once these microbes have breached physical barriers such as the skin or intestinal tract mucosa they are recognized by TLRs which activate immune cell responses The TLRs include TLR1 TLR2 TLR3 TLR4 TLR5 TLR6 TLR7 TLR8 TLR9 TLR10TLR11 TLR12 and TLR13 though the latter two are not found in humans
Levamisole marketed under the trade name Ergamisol is a medication used to treat parasitic worm infections It has also been studied as a method to stimulate the immune system as part of the treatment of cancer Most current commercial preparations are intended for veterinary use as a dewormer in cattle pigs and sheep
After being pulled from the market in the US and Canada in 1999 and 2003 respectively levamisole has been tested in combination with fluorouracil to treat colon cancer Evidence from clinical trials support its addition to fluorouracil therapy to benefit patients with colon cancer
One of the more serious side effects of Levamisole is agranulocytosis or the depletion of the white blood cells In particular neutrophils appear to be affected the most This occurs in 008-5 of the studied populations
There have also been reports of levamisole induced necrosis syndrome in which erythematous painful papules can appear almost anywhere on skin
Levamisole was evaluated as
an immune stimulant in a
randomized controlled study
of patients with anaplastic
gliomas who had undergone
surgical resection and who
were also treated with
radiotherapy and BCNU chemotherapy
Studies utilizing the avian sarcoma virus-induced glioma in rats also showed no
improvement in survival with levamisole stimulation as the only immune agent but
the combination of active immunization and adjuvant stimulation with bacillus
Calmette-Guerin plus levamisole was found to be therapeutically effective in this model and will be used in future pilot studies of active immunization in patients
Levamisole is a synthetic phenylimidazolthiazole that was first introduced in 1966 as an anti-helmintic agent
Current studies have been focused upon its effect on immune response and on cancer treatment
We examined the molecular mechanisms of levamisole in the activation and maturation of human
monocyte-derived dendritic cells (DC) and human T cells
Treatment of DC with levamisole increased the presentation of CD80 CD86 CD83 and human
leucocyte antigen D-related (HLA-DR) molecules on the cell membrane as well as the production of
interleukin-12 p40 and IL-10
Levamisole-treated human DC also enhanced T cell activation towards type 1 T helper immune
response by inducing interferon-γ secretion Neutralization with antibodies against Toll-like receptor
(TLR)-2 inhibited levamisole-induced production of IL-12 p40 and IL-10 suggesting a vital role for TLR-2
in signalling DC upon incubation with levamisole
In this study we showed that BALBc bone marrow-derived DC stimulated with LMS resulted in enhanced cell-
surface expression of CD80 CD86 CD40 and MHC class II as well as enhanced production of IL-12p70 TNF-α
and IL-1β Interestingly the LMS activated DCs were able to stimulate CD4(+) T cell proliferation and facilitated
Th1 differentiation by increasing the secretion of IFN-γ in an allogeneic mixed leukocyte reaction Furthermore to
confirm the in vitro data we investigated the effect of LMS on antigen-specific antibody and cytokine
production in BALBc mice Immunization with LMS plus OVA showed that anti-OVA IgG2a and IFN-γ were
increased significantly compared with OVA alone in BALBc mice
bull Aliment Pharmacol Ther 2010 Sep32(6)756-62 Meta-analysis levamisole improves the immune response to hepatitisBvaccine in dialysis patients
bull Fabrizi F1 Dixit V Messa P Martin P
bull We identified four studies involving 328 unique patients on regular dialysis Only prospective randomized clinical trials (RCTs) were included
bull Pooling of study results showed a significant increase in response rates among study (levamisole plus HBV vaccine) vs control (HBV vaccine alone) patients the pooled Odds Ratio was 2432 (95 Confidence Intervals 134 4403) P = 0002
bull Nephrology (Carlton) 2014 Jan19(1)27-31 Effectof levamisole supplementation on tetanus vaccination response rates in haemodialysis patients a randomized double-blind placebo-controlledtrial Fallahzadeh MK1 Sajjadi S Singh N Khajeh M Sagheb MM
bull At 6 months 11 out of 15 (73) patients in the levamisole group as compared with four out of 16 (25) patients in the placebo group still had protective anti-tetanus IgG levels (relative riskthinsp=thinsp293 95 CIthinsp=thinsp119 723)
bull Supplementation of Td vaccination with levamisole may enhance seroconversion against tetanus in haemodialysis patients
BCG is an attenuated (nonvirulent) form of Mycobacterium bovis cultured in 1921 by Albert Calmette and Camille Guerin at the Pasteur Institute in Lille France In the late 1920rsquos autopsy studies performed at Johns Hopkins Hospital in Baltimore Maryland showed a lower frequency of cancer in patients with tuberculosis
Attempts were made to use BCG against a variety of human cancer tumors with only limited success It wasnrsquot until the 1970rsquos however that a Canadian urologist Dr Alvaro Morales began his groundbreaking work on the use of intravesical BCG for the treatment of superficial bladder cancer Over 30 years later BCG continues to be used worldwide for the treatment of high grade noninvasive bladder cancer
Mycobacterium bovis (TEM)
We investigated whether three mycobacterial preparations currently used in the clinic (BCG and heat-killed Mycobacterium vaccae and Mycobacterium obuense) can stimulate anti-tumoureffector responses in human γδ T-cells Results show that γδ T-cells are activated by these mycobacterial preparations as indicated by upregulation of activation marker expression and proliferation
Activated γδ T-cells display enhanced effector responses as shown by upregulated granzyme B expression production of the T(H)1 cytokines IFN-γ and TNF-α and enhanced degranulation in response to susceptible and resistant tumour cells
A type of metastasis in which skin cancer spreads through a lymph vessel and begins to grow more than 2 centimeters away from the primary tumor but before it reaches the nearest lymph node
For the small uncontrolled study twenty (20) patients in advanced stages with limited life expectancy were recruited in a 2-year period Patients were classified into two groups according to the treatment to be employed Group 1 included 6 patients who refused to be treated with standard treatments and received only immunotherapy Group 2 included 14 patients treated with both immunotherapy and chemotherapyradiotherapy (CTRT) The vaccination procedure 3 intradermal doses of 05 ml each with intervals of 6 weeks between each dose Tumor fragments (about 1 g) from patients were kept in sterile PBS at minus80 degC until use For each dose about 03ndash04 g of tumor tissue were macerated in 06 ml sterile PBS
At the moment of vaccination the soluble fraction of the homogenate was mixed with formaldehyde 36 at a final concentration of 002 and 06 ml of BCG suspension 015
The survival rate upon a 5-year period was plotted for the immunotherapy only (IT) group and the combined treated (CTRTIT) group as well as for the overall survival across all subjects The calculated 5-year survival is indicated for each plot
However γδ T cells are peculiar in that they do not seem to require antigen processing and major-histocompatibility-complex (MHC) presentation of peptide epitopes although some recognize MHC class Ib molecules Furthermore γδ T cells are believed to have a prominent role in recognition of lipid antigens
Imiquimod
Imiquimod (INN) is a prescription medication that acts as an immune response modifier and is used to treat genital warts superficial basal cell carcinoma and actinic keratosis Imiquimod signals to the innate arm of the immune system through the toll-like receptor 7 (TLR7)
Plasmacytoid dendritic cells (pDCs) are innate immune cells that circulate in the blood and are found in peripheral lymphoid organs They constitute lt 04 of peripheral blood mononuclear cells (PBMC) In humans these cells express the surface markers CD123 BDCA-2(CD303) and BDCA-4 (CD304) but do not express high levels of CD11c or CD14 which distinguishes them from conventional dendritic cells or monocytes respectively
TNF-related apoptosis-inducing ligand (TRAIL) is aprotein functioning as a ligand that induces the process of cell death called apoptosis TRAIL is a cytokine that is produced and secreted by most normal tissue cells It causes apoptosis primarily in tumor cells by binding to certain death receptors TRAIL has also been designated CD253 (cluster of differentiation 253)
Melanoma in situ ndash Lentigo malignaImiquimod Treatment
Mifamurtide (Mepactreg Takeda) is a drug against osteosarcoma
mainly affecting children and young adults which is lethal in about a third of cases The drug was approved in Europe in March 2009
In a phase-III clinical trial in about 800 newly diagnosed osteosarcoma patients
mifamurtide was combined with the chemotherapeutic agents doxorubicin and
methotrexate with or without cisplatin and ifosfamide The mortality could be lowered
by 30 versus chemotherapy plus placebo Six years after the treatment 78 of patients were alive Drugs in RampD 9 (2) 131ndash5 2008
Looking to the past may help planning for thefuture
Experiments showed that CCL3 upregulation in the skin was dependent on the induction of the Td recall response and was significantly reduced by CD4+ T cell depletion
bull Toll-like receptors (TLRs) are a class of proteins that play a key role in the innate immune system They are single membrane-spanning non-catalytic receptors usually expressed in sentinel cells such as macrophages and dendritic cells that recognize structurally conserved molecules derived from microbes Once these microbes have breached physical barriers such as the skin or intestinal tract mucosa they are recognized by TLRs which activate immune cell responses The TLRs include TLR1 TLR2 TLR3 TLR4 TLR5 TLR6 TLR7 TLR8 TLR9 TLR10TLR11 TLR12 and TLR13 though the latter two are not found in humans
Levamisole marketed under the trade name Ergamisol is a medication used to treat parasitic worm infections It has also been studied as a method to stimulate the immune system as part of the treatment of cancer Most current commercial preparations are intended for veterinary use as a dewormer in cattle pigs and sheep
After being pulled from the market in the US and Canada in 1999 and 2003 respectively levamisole has been tested in combination with fluorouracil to treat colon cancer Evidence from clinical trials support its addition to fluorouracil therapy to benefit patients with colon cancer
One of the more serious side effects of Levamisole is agranulocytosis or the depletion of the white blood cells In particular neutrophils appear to be affected the most This occurs in 008-5 of the studied populations
There have also been reports of levamisole induced necrosis syndrome in which erythematous painful papules can appear almost anywhere on skin
Levamisole was evaluated as
an immune stimulant in a
randomized controlled study
of patients with anaplastic
gliomas who had undergone
surgical resection and who
were also treated with
radiotherapy and BCNU chemotherapy
Studies utilizing the avian sarcoma virus-induced glioma in rats also showed no
improvement in survival with levamisole stimulation as the only immune agent but
the combination of active immunization and adjuvant stimulation with bacillus
Calmette-Guerin plus levamisole was found to be therapeutically effective in this model and will be used in future pilot studies of active immunization in patients
Levamisole is a synthetic phenylimidazolthiazole that was first introduced in 1966 as an anti-helmintic agent
Current studies have been focused upon its effect on immune response and on cancer treatment
We examined the molecular mechanisms of levamisole in the activation and maturation of human
monocyte-derived dendritic cells (DC) and human T cells
Treatment of DC with levamisole increased the presentation of CD80 CD86 CD83 and human
leucocyte antigen D-related (HLA-DR) molecules on the cell membrane as well as the production of
interleukin-12 p40 and IL-10
Levamisole-treated human DC also enhanced T cell activation towards type 1 T helper immune
response by inducing interferon-γ secretion Neutralization with antibodies against Toll-like receptor
(TLR)-2 inhibited levamisole-induced production of IL-12 p40 and IL-10 suggesting a vital role for TLR-2
in signalling DC upon incubation with levamisole
In this study we showed that BALBc bone marrow-derived DC stimulated with LMS resulted in enhanced cell-
surface expression of CD80 CD86 CD40 and MHC class II as well as enhanced production of IL-12p70 TNF-α
and IL-1β Interestingly the LMS activated DCs were able to stimulate CD4(+) T cell proliferation and facilitated
Th1 differentiation by increasing the secretion of IFN-γ in an allogeneic mixed leukocyte reaction Furthermore to
confirm the in vitro data we investigated the effect of LMS on antigen-specific antibody and cytokine
production in BALBc mice Immunization with LMS plus OVA showed that anti-OVA IgG2a and IFN-γ were
increased significantly compared with OVA alone in BALBc mice
bull Aliment Pharmacol Ther 2010 Sep32(6)756-62 Meta-analysis levamisole improves the immune response to hepatitisBvaccine in dialysis patients
bull Fabrizi F1 Dixit V Messa P Martin P
bull We identified four studies involving 328 unique patients on regular dialysis Only prospective randomized clinical trials (RCTs) were included
bull Pooling of study results showed a significant increase in response rates among study (levamisole plus HBV vaccine) vs control (HBV vaccine alone) patients the pooled Odds Ratio was 2432 (95 Confidence Intervals 134 4403) P = 0002
bull Nephrology (Carlton) 2014 Jan19(1)27-31 Effectof levamisole supplementation on tetanus vaccination response rates in haemodialysis patients a randomized double-blind placebo-controlledtrial Fallahzadeh MK1 Sajjadi S Singh N Khajeh M Sagheb MM
bull At 6 months 11 out of 15 (73) patients in the levamisole group as compared with four out of 16 (25) patients in the placebo group still had protective anti-tetanus IgG levels (relative riskthinsp=thinsp293 95 CIthinsp=thinsp119 723)
bull Supplementation of Td vaccination with levamisole may enhance seroconversion against tetanus in haemodialysis patients
BCG is an attenuated (nonvirulent) form of Mycobacterium bovis cultured in 1921 by Albert Calmette and Camille Guerin at the Pasteur Institute in Lille France In the late 1920rsquos autopsy studies performed at Johns Hopkins Hospital in Baltimore Maryland showed a lower frequency of cancer in patients with tuberculosis
Attempts were made to use BCG against a variety of human cancer tumors with only limited success It wasnrsquot until the 1970rsquos however that a Canadian urologist Dr Alvaro Morales began his groundbreaking work on the use of intravesical BCG for the treatment of superficial bladder cancer Over 30 years later BCG continues to be used worldwide for the treatment of high grade noninvasive bladder cancer
Mycobacterium bovis (TEM)
We investigated whether three mycobacterial preparations currently used in the clinic (BCG and heat-killed Mycobacterium vaccae and Mycobacterium obuense) can stimulate anti-tumoureffector responses in human γδ T-cells Results show that γδ T-cells are activated by these mycobacterial preparations as indicated by upregulation of activation marker expression and proliferation
Activated γδ T-cells display enhanced effector responses as shown by upregulated granzyme B expression production of the T(H)1 cytokines IFN-γ and TNF-α and enhanced degranulation in response to susceptible and resistant tumour cells
A type of metastasis in which skin cancer spreads through a lymph vessel and begins to grow more than 2 centimeters away from the primary tumor but before it reaches the nearest lymph node
For the small uncontrolled study twenty (20) patients in advanced stages with limited life expectancy were recruited in a 2-year period Patients were classified into two groups according to the treatment to be employed Group 1 included 6 patients who refused to be treated with standard treatments and received only immunotherapy Group 2 included 14 patients treated with both immunotherapy and chemotherapyradiotherapy (CTRT) The vaccination procedure 3 intradermal doses of 05 ml each with intervals of 6 weeks between each dose Tumor fragments (about 1 g) from patients were kept in sterile PBS at minus80 degC until use For each dose about 03ndash04 g of tumor tissue were macerated in 06 ml sterile PBS
At the moment of vaccination the soluble fraction of the homogenate was mixed with formaldehyde 36 at a final concentration of 002 and 06 ml of BCG suspension 015
The survival rate upon a 5-year period was plotted for the immunotherapy only (IT) group and the combined treated (CTRTIT) group as well as for the overall survival across all subjects The calculated 5-year survival is indicated for each plot
However γδ T cells are peculiar in that they do not seem to require antigen processing and major-histocompatibility-complex (MHC) presentation of peptide epitopes although some recognize MHC class Ib molecules Furthermore γδ T cells are believed to have a prominent role in recognition of lipid antigens
Imiquimod
Imiquimod (INN) is a prescription medication that acts as an immune response modifier and is used to treat genital warts superficial basal cell carcinoma and actinic keratosis Imiquimod signals to the innate arm of the immune system through the toll-like receptor 7 (TLR7)
Plasmacytoid dendritic cells (pDCs) are innate immune cells that circulate in the blood and are found in peripheral lymphoid organs They constitute lt 04 of peripheral blood mononuclear cells (PBMC) In humans these cells express the surface markers CD123 BDCA-2(CD303) and BDCA-4 (CD304) but do not express high levels of CD11c or CD14 which distinguishes them from conventional dendritic cells or monocytes respectively
TNF-related apoptosis-inducing ligand (TRAIL) is aprotein functioning as a ligand that induces the process of cell death called apoptosis TRAIL is a cytokine that is produced and secreted by most normal tissue cells It causes apoptosis primarily in tumor cells by binding to certain death receptors TRAIL has also been designated CD253 (cluster of differentiation 253)
Melanoma in situ ndash Lentigo malignaImiquimod Treatment
Mifamurtide (Mepactreg Takeda) is a drug against osteosarcoma
mainly affecting children and young adults which is lethal in about a third of cases The drug was approved in Europe in March 2009
In a phase-III clinical trial in about 800 newly diagnosed osteosarcoma patients
mifamurtide was combined with the chemotherapeutic agents doxorubicin and
methotrexate with or without cisplatin and ifosfamide The mortality could be lowered
by 30 versus chemotherapy plus placebo Six years after the treatment 78 of patients were alive Drugs in RampD 9 (2) 131ndash5 2008
Looking to the past may help planning for thefuture
bull Toll-like receptors (TLRs) are a class of proteins that play a key role in the innate immune system They are single membrane-spanning non-catalytic receptors usually expressed in sentinel cells such as macrophages and dendritic cells that recognize structurally conserved molecules derived from microbes Once these microbes have breached physical barriers such as the skin or intestinal tract mucosa they are recognized by TLRs which activate immune cell responses The TLRs include TLR1 TLR2 TLR3 TLR4 TLR5 TLR6 TLR7 TLR8 TLR9 TLR10TLR11 TLR12 and TLR13 though the latter two are not found in humans
Levamisole marketed under the trade name Ergamisol is a medication used to treat parasitic worm infections It has also been studied as a method to stimulate the immune system as part of the treatment of cancer Most current commercial preparations are intended for veterinary use as a dewormer in cattle pigs and sheep
After being pulled from the market in the US and Canada in 1999 and 2003 respectively levamisole has been tested in combination with fluorouracil to treat colon cancer Evidence from clinical trials support its addition to fluorouracil therapy to benefit patients with colon cancer
One of the more serious side effects of Levamisole is agranulocytosis or the depletion of the white blood cells In particular neutrophils appear to be affected the most This occurs in 008-5 of the studied populations
There have also been reports of levamisole induced necrosis syndrome in which erythematous painful papules can appear almost anywhere on skin
Levamisole was evaluated as
an immune stimulant in a
randomized controlled study
of patients with anaplastic
gliomas who had undergone
surgical resection and who
were also treated with
radiotherapy and BCNU chemotherapy
Studies utilizing the avian sarcoma virus-induced glioma in rats also showed no
improvement in survival with levamisole stimulation as the only immune agent but
the combination of active immunization and adjuvant stimulation with bacillus
Calmette-Guerin plus levamisole was found to be therapeutically effective in this model and will be used in future pilot studies of active immunization in patients
Levamisole is a synthetic phenylimidazolthiazole that was first introduced in 1966 as an anti-helmintic agent
Current studies have been focused upon its effect on immune response and on cancer treatment
We examined the molecular mechanisms of levamisole in the activation and maturation of human
monocyte-derived dendritic cells (DC) and human T cells
Treatment of DC with levamisole increased the presentation of CD80 CD86 CD83 and human
leucocyte antigen D-related (HLA-DR) molecules on the cell membrane as well as the production of
interleukin-12 p40 and IL-10
Levamisole-treated human DC also enhanced T cell activation towards type 1 T helper immune
response by inducing interferon-γ secretion Neutralization with antibodies against Toll-like receptor
(TLR)-2 inhibited levamisole-induced production of IL-12 p40 and IL-10 suggesting a vital role for TLR-2
in signalling DC upon incubation with levamisole
In this study we showed that BALBc bone marrow-derived DC stimulated with LMS resulted in enhanced cell-
surface expression of CD80 CD86 CD40 and MHC class II as well as enhanced production of IL-12p70 TNF-α
and IL-1β Interestingly the LMS activated DCs were able to stimulate CD4(+) T cell proliferation and facilitated
Th1 differentiation by increasing the secretion of IFN-γ in an allogeneic mixed leukocyte reaction Furthermore to
confirm the in vitro data we investigated the effect of LMS on antigen-specific antibody and cytokine
production in BALBc mice Immunization with LMS plus OVA showed that anti-OVA IgG2a and IFN-γ were
increased significantly compared with OVA alone in BALBc mice
bull Aliment Pharmacol Ther 2010 Sep32(6)756-62 Meta-analysis levamisole improves the immune response to hepatitisBvaccine in dialysis patients
bull Fabrizi F1 Dixit V Messa P Martin P
bull We identified four studies involving 328 unique patients on regular dialysis Only prospective randomized clinical trials (RCTs) were included
bull Pooling of study results showed a significant increase in response rates among study (levamisole plus HBV vaccine) vs control (HBV vaccine alone) patients the pooled Odds Ratio was 2432 (95 Confidence Intervals 134 4403) P = 0002
bull Nephrology (Carlton) 2014 Jan19(1)27-31 Effectof levamisole supplementation on tetanus vaccination response rates in haemodialysis patients a randomized double-blind placebo-controlledtrial Fallahzadeh MK1 Sajjadi S Singh N Khajeh M Sagheb MM
bull At 6 months 11 out of 15 (73) patients in the levamisole group as compared with four out of 16 (25) patients in the placebo group still had protective anti-tetanus IgG levels (relative riskthinsp=thinsp293 95 CIthinsp=thinsp119 723)
bull Supplementation of Td vaccination with levamisole may enhance seroconversion against tetanus in haemodialysis patients
BCG is an attenuated (nonvirulent) form of Mycobacterium bovis cultured in 1921 by Albert Calmette and Camille Guerin at the Pasteur Institute in Lille France In the late 1920rsquos autopsy studies performed at Johns Hopkins Hospital in Baltimore Maryland showed a lower frequency of cancer in patients with tuberculosis
Attempts were made to use BCG against a variety of human cancer tumors with only limited success It wasnrsquot until the 1970rsquos however that a Canadian urologist Dr Alvaro Morales began his groundbreaking work on the use of intravesical BCG for the treatment of superficial bladder cancer Over 30 years later BCG continues to be used worldwide for the treatment of high grade noninvasive bladder cancer
Mycobacterium bovis (TEM)
We investigated whether three mycobacterial preparations currently used in the clinic (BCG and heat-killed Mycobacterium vaccae and Mycobacterium obuense) can stimulate anti-tumoureffector responses in human γδ T-cells Results show that γδ T-cells are activated by these mycobacterial preparations as indicated by upregulation of activation marker expression and proliferation
Activated γδ T-cells display enhanced effector responses as shown by upregulated granzyme B expression production of the T(H)1 cytokines IFN-γ and TNF-α and enhanced degranulation in response to susceptible and resistant tumour cells
A type of metastasis in which skin cancer spreads through a lymph vessel and begins to grow more than 2 centimeters away from the primary tumor but before it reaches the nearest lymph node
For the small uncontrolled study twenty (20) patients in advanced stages with limited life expectancy were recruited in a 2-year period Patients were classified into two groups according to the treatment to be employed Group 1 included 6 patients who refused to be treated with standard treatments and received only immunotherapy Group 2 included 14 patients treated with both immunotherapy and chemotherapyradiotherapy (CTRT) The vaccination procedure 3 intradermal doses of 05 ml each with intervals of 6 weeks between each dose Tumor fragments (about 1 g) from patients were kept in sterile PBS at minus80 degC until use For each dose about 03ndash04 g of tumor tissue were macerated in 06 ml sterile PBS
At the moment of vaccination the soluble fraction of the homogenate was mixed with formaldehyde 36 at a final concentration of 002 and 06 ml of BCG suspension 015
The survival rate upon a 5-year period was plotted for the immunotherapy only (IT) group and the combined treated (CTRTIT) group as well as for the overall survival across all subjects The calculated 5-year survival is indicated for each plot
However γδ T cells are peculiar in that they do not seem to require antigen processing and major-histocompatibility-complex (MHC) presentation of peptide epitopes although some recognize MHC class Ib molecules Furthermore γδ T cells are believed to have a prominent role in recognition of lipid antigens
Imiquimod
Imiquimod (INN) is a prescription medication that acts as an immune response modifier and is used to treat genital warts superficial basal cell carcinoma and actinic keratosis Imiquimod signals to the innate arm of the immune system through the toll-like receptor 7 (TLR7)
Plasmacytoid dendritic cells (pDCs) are innate immune cells that circulate in the blood and are found in peripheral lymphoid organs They constitute lt 04 of peripheral blood mononuclear cells (PBMC) In humans these cells express the surface markers CD123 BDCA-2(CD303) and BDCA-4 (CD304) but do not express high levels of CD11c or CD14 which distinguishes them from conventional dendritic cells or monocytes respectively
TNF-related apoptosis-inducing ligand (TRAIL) is aprotein functioning as a ligand that induces the process of cell death called apoptosis TRAIL is a cytokine that is produced and secreted by most normal tissue cells It causes apoptosis primarily in tumor cells by binding to certain death receptors TRAIL has also been designated CD253 (cluster of differentiation 253)
Melanoma in situ ndash Lentigo malignaImiquimod Treatment
Mifamurtide (Mepactreg Takeda) is a drug against osteosarcoma
mainly affecting children and young adults which is lethal in about a third of cases The drug was approved in Europe in March 2009
In a phase-III clinical trial in about 800 newly diagnosed osteosarcoma patients
mifamurtide was combined with the chemotherapeutic agents doxorubicin and
methotrexate with or without cisplatin and ifosfamide The mortality could be lowered
by 30 versus chemotherapy plus placebo Six years after the treatment 78 of patients were alive Drugs in RampD 9 (2) 131ndash5 2008
Looking to the past may help planning for thefuture
Levamisole marketed under the trade name Ergamisol is a medication used to treat parasitic worm infections It has also been studied as a method to stimulate the immune system as part of the treatment of cancer Most current commercial preparations are intended for veterinary use as a dewormer in cattle pigs and sheep
After being pulled from the market in the US and Canada in 1999 and 2003 respectively levamisole has been tested in combination with fluorouracil to treat colon cancer Evidence from clinical trials support its addition to fluorouracil therapy to benefit patients with colon cancer
One of the more serious side effects of Levamisole is agranulocytosis or the depletion of the white blood cells In particular neutrophils appear to be affected the most This occurs in 008-5 of the studied populations
There have also been reports of levamisole induced necrosis syndrome in which erythematous painful papules can appear almost anywhere on skin
Levamisole was evaluated as
an immune stimulant in a
randomized controlled study
of patients with anaplastic
gliomas who had undergone
surgical resection and who
were also treated with
radiotherapy and BCNU chemotherapy
Studies utilizing the avian sarcoma virus-induced glioma in rats also showed no
improvement in survival with levamisole stimulation as the only immune agent but
the combination of active immunization and adjuvant stimulation with bacillus
Calmette-Guerin plus levamisole was found to be therapeutically effective in this model and will be used in future pilot studies of active immunization in patients
Levamisole is a synthetic phenylimidazolthiazole that was first introduced in 1966 as an anti-helmintic agent
Current studies have been focused upon its effect on immune response and on cancer treatment
We examined the molecular mechanisms of levamisole in the activation and maturation of human
monocyte-derived dendritic cells (DC) and human T cells
Treatment of DC with levamisole increased the presentation of CD80 CD86 CD83 and human
leucocyte antigen D-related (HLA-DR) molecules on the cell membrane as well as the production of
interleukin-12 p40 and IL-10
Levamisole-treated human DC also enhanced T cell activation towards type 1 T helper immune
response by inducing interferon-γ secretion Neutralization with antibodies against Toll-like receptor
(TLR)-2 inhibited levamisole-induced production of IL-12 p40 and IL-10 suggesting a vital role for TLR-2
in signalling DC upon incubation with levamisole
In this study we showed that BALBc bone marrow-derived DC stimulated with LMS resulted in enhanced cell-
surface expression of CD80 CD86 CD40 and MHC class II as well as enhanced production of IL-12p70 TNF-α
and IL-1β Interestingly the LMS activated DCs were able to stimulate CD4(+) T cell proliferation and facilitated
Th1 differentiation by increasing the secretion of IFN-γ in an allogeneic mixed leukocyte reaction Furthermore to
confirm the in vitro data we investigated the effect of LMS on antigen-specific antibody and cytokine
production in BALBc mice Immunization with LMS plus OVA showed that anti-OVA IgG2a and IFN-γ were
increased significantly compared with OVA alone in BALBc mice
bull Aliment Pharmacol Ther 2010 Sep32(6)756-62 Meta-analysis levamisole improves the immune response to hepatitisBvaccine in dialysis patients
bull Fabrizi F1 Dixit V Messa P Martin P
bull We identified four studies involving 328 unique patients on regular dialysis Only prospective randomized clinical trials (RCTs) were included
bull Pooling of study results showed a significant increase in response rates among study (levamisole plus HBV vaccine) vs control (HBV vaccine alone) patients the pooled Odds Ratio was 2432 (95 Confidence Intervals 134 4403) P = 0002
bull Nephrology (Carlton) 2014 Jan19(1)27-31 Effectof levamisole supplementation on tetanus vaccination response rates in haemodialysis patients a randomized double-blind placebo-controlledtrial Fallahzadeh MK1 Sajjadi S Singh N Khajeh M Sagheb MM
bull At 6 months 11 out of 15 (73) patients in the levamisole group as compared with four out of 16 (25) patients in the placebo group still had protective anti-tetanus IgG levels (relative riskthinsp=thinsp293 95 CIthinsp=thinsp119 723)
bull Supplementation of Td vaccination with levamisole may enhance seroconversion against tetanus in haemodialysis patients
BCG is an attenuated (nonvirulent) form of Mycobacterium bovis cultured in 1921 by Albert Calmette and Camille Guerin at the Pasteur Institute in Lille France In the late 1920rsquos autopsy studies performed at Johns Hopkins Hospital in Baltimore Maryland showed a lower frequency of cancer in patients with tuberculosis
Attempts were made to use BCG against a variety of human cancer tumors with only limited success It wasnrsquot until the 1970rsquos however that a Canadian urologist Dr Alvaro Morales began his groundbreaking work on the use of intravesical BCG for the treatment of superficial bladder cancer Over 30 years later BCG continues to be used worldwide for the treatment of high grade noninvasive bladder cancer
Mycobacterium bovis (TEM)
We investigated whether three mycobacterial preparations currently used in the clinic (BCG and heat-killed Mycobacterium vaccae and Mycobacterium obuense) can stimulate anti-tumoureffector responses in human γδ T-cells Results show that γδ T-cells are activated by these mycobacterial preparations as indicated by upregulation of activation marker expression and proliferation
Activated γδ T-cells display enhanced effector responses as shown by upregulated granzyme B expression production of the T(H)1 cytokines IFN-γ and TNF-α and enhanced degranulation in response to susceptible and resistant tumour cells
A type of metastasis in which skin cancer spreads through a lymph vessel and begins to grow more than 2 centimeters away from the primary tumor but before it reaches the nearest lymph node
For the small uncontrolled study twenty (20) patients in advanced stages with limited life expectancy were recruited in a 2-year period Patients were classified into two groups according to the treatment to be employed Group 1 included 6 patients who refused to be treated with standard treatments and received only immunotherapy Group 2 included 14 patients treated with both immunotherapy and chemotherapyradiotherapy (CTRT) The vaccination procedure 3 intradermal doses of 05 ml each with intervals of 6 weeks between each dose Tumor fragments (about 1 g) from patients were kept in sterile PBS at minus80 degC until use For each dose about 03ndash04 g of tumor tissue were macerated in 06 ml sterile PBS
At the moment of vaccination the soluble fraction of the homogenate was mixed with formaldehyde 36 at a final concentration of 002 and 06 ml of BCG suspension 015
The survival rate upon a 5-year period was plotted for the immunotherapy only (IT) group and the combined treated (CTRTIT) group as well as for the overall survival across all subjects The calculated 5-year survival is indicated for each plot
However γδ T cells are peculiar in that they do not seem to require antigen processing and major-histocompatibility-complex (MHC) presentation of peptide epitopes although some recognize MHC class Ib molecules Furthermore γδ T cells are believed to have a prominent role in recognition of lipid antigens
Imiquimod
Imiquimod (INN) is a prescription medication that acts as an immune response modifier and is used to treat genital warts superficial basal cell carcinoma and actinic keratosis Imiquimod signals to the innate arm of the immune system through the toll-like receptor 7 (TLR7)
Plasmacytoid dendritic cells (pDCs) are innate immune cells that circulate in the blood and are found in peripheral lymphoid organs They constitute lt 04 of peripheral blood mononuclear cells (PBMC) In humans these cells express the surface markers CD123 BDCA-2(CD303) and BDCA-4 (CD304) but do not express high levels of CD11c or CD14 which distinguishes them from conventional dendritic cells or monocytes respectively
TNF-related apoptosis-inducing ligand (TRAIL) is aprotein functioning as a ligand that induces the process of cell death called apoptosis TRAIL is a cytokine that is produced and secreted by most normal tissue cells It causes apoptosis primarily in tumor cells by binding to certain death receptors TRAIL has also been designated CD253 (cluster of differentiation 253)
Melanoma in situ ndash Lentigo malignaImiquimod Treatment
Mifamurtide (Mepactreg Takeda) is a drug against osteosarcoma
mainly affecting children and young adults which is lethal in about a third of cases The drug was approved in Europe in March 2009
In a phase-III clinical trial in about 800 newly diagnosed osteosarcoma patients
mifamurtide was combined with the chemotherapeutic agents doxorubicin and
methotrexate with or without cisplatin and ifosfamide The mortality could be lowered
by 30 versus chemotherapy plus placebo Six years after the treatment 78 of patients were alive Drugs in RampD 9 (2) 131ndash5 2008
Looking to the past may help planning for thefuture
One of the more serious side effects of Levamisole is agranulocytosis or the depletion of the white blood cells In particular neutrophils appear to be affected the most This occurs in 008-5 of the studied populations
There have also been reports of levamisole induced necrosis syndrome in which erythematous painful papules can appear almost anywhere on skin
Levamisole was evaluated as
an immune stimulant in a
randomized controlled study
of patients with anaplastic
gliomas who had undergone
surgical resection and who
were also treated with
radiotherapy and BCNU chemotherapy
Studies utilizing the avian sarcoma virus-induced glioma in rats also showed no
improvement in survival with levamisole stimulation as the only immune agent but
the combination of active immunization and adjuvant stimulation with bacillus
Calmette-Guerin plus levamisole was found to be therapeutically effective in this model and will be used in future pilot studies of active immunization in patients
Levamisole is a synthetic phenylimidazolthiazole that was first introduced in 1966 as an anti-helmintic agent
Current studies have been focused upon its effect on immune response and on cancer treatment
We examined the molecular mechanisms of levamisole in the activation and maturation of human
monocyte-derived dendritic cells (DC) and human T cells
Treatment of DC with levamisole increased the presentation of CD80 CD86 CD83 and human
leucocyte antigen D-related (HLA-DR) molecules on the cell membrane as well as the production of
interleukin-12 p40 and IL-10
Levamisole-treated human DC also enhanced T cell activation towards type 1 T helper immune
response by inducing interferon-γ secretion Neutralization with antibodies against Toll-like receptor
(TLR)-2 inhibited levamisole-induced production of IL-12 p40 and IL-10 suggesting a vital role for TLR-2
in signalling DC upon incubation with levamisole
In this study we showed that BALBc bone marrow-derived DC stimulated with LMS resulted in enhanced cell-
surface expression of CD80 CD86 CD40 and MHC class II as well as enhanced production of IL-12p70 TNF-α
and IL-1β Interestingly the LMS activated DCs were able to stimulate CD4(+) T cell proliferation and facilitated
Th1 differentiation by increasing the secretion of IFN-γ in an allogeneic mixed leukocyte reaction Furthermore to
confirm the in vitro data we investigated the effect of LMS on antigen-specific antibody and cytokine
production in BALBc mice Immunization with LMS plus OVA showed that anti-OVA IgG2a and IFN-γ were
increased significantly compared with OVA alone in BALBc mice
bull Aliment Pharmacol Ther 2010 Sep32(6)756-62 Meta-analysis levamisole improves the immune response to hepatitisBvaccine in dialysis patients
bull Fabrizi F1 Dixit V Messa P Martin P
bull We identified four studies involving 328 unique patients on regular dialysis Only prospective randomized clinical trials (RCTs) were included
bull Pooling of study results showed a significant increase in response rates among study (levamisole plus HBV vaccine) vs control (HBV vaccine alone) patients the pooled Odds Ratio was 2432 (95 Confidence Intervals 134 4403) P = 0002
bull Nephrology (Carlton) 2014 Jan19(1)27-31 Effectof levamisole supplementation on tetanus vaccination response rates in haemodialysis patients a randomized double-blind placebo-controlledtrial Fallahzadeh MK1 Sajjadi S Singh N Khajeh M Sagheb MM
bull At 6 months 11 out of 15 (73) patients in the levamisole group as compared with four out of 16 (25) patients in the placebo group still had protective anti-tetanus IgG levels (relative riskthinsp=thinsp293 95 CIthinsp=thinsp119 723)
bull Supplementation of Td vaccination with levamisole may enhance seroconversion against tetanus in haemodialysis patients
BCG is an attenuated (nonvirulent) form of Mycobacterium bovis cultured in 1921 by Albert Calmette and Camille Guerin at the Pasteur Institute in Lille France In the late 1920rsquos autopsy studies performed at Johns Hopkins Hospital in Baltimore Maryland showed a lower frequency of cancer in patients with tuberculosis
Attempts were made to use BCG against a variety of human cancer tumors with only limited success It wasnrsquot until the 1970rsquos however that a Canadian urologist Dr Alvaro Morales began his groundbreaking work on the use of intravesical BCG for the treatment of superficial bladder cancer Over 30 years later BCG continues to be used worldwide for the treatment of high grade noninvasive bladder cancer
Mycobacterium bovis (TEM)
We investigated whether three mycobacterial preparations currently used in the clinic (BCG and heat-killed Mycobacterium vaccae and Mycobacterium obuense) can stimulate anti-tumoureffector responses in human γδ T-cells Results show that γδ T-cells are activated by these mycobacterial preparations as indicated by upregulation of activation marker expression and proliferation
Activated γδ T-cells display enhanced effector responses as shown by upregulated granzyme B expression production of the T(H)1 cytokines IFN-γ and TNF-α and enhanced degranulation in response to susceptible and resistant tumour cells
A type of metastasis in which skin cancer spreads through a lymph vessel and begins to grow more than 2 centimeters away from the primary tumor but before it reaches the nearest lymph node
For the small uncontrolled study twenty (20) patients in advanced stages with limited life expectancy were recruited in a 2-year period Patients were classified into two groups according to the treatment to be employed Group 1 included 6 patients who refused to be treated with standard treatments and received only immunotherapy Group 2 included 14 patients treated with both immunotherapy and chemotherapyradiotherapy (CTRT) The vaccination procedure 3 intradermal doses of 05 ml each with intervals of 6 weeks between each dose Tumor fragments (about 1 g) from patients were kept in sterile PBS at minus80 degC until use For each dose about 03ndash04 g of tumor tissue were macerated in 06 ml sterile PBS
At the moment of vaccination the soluble fraction of the homogenate was mixed with formaldehyde 36 at a final concentration of 002 and 06 ml of BCG suspension 015
The survival rate upon a 5-year period was plotted for the immunotherapy only (IT) group and the combined treated (CTRTIT) group as well as for the overall survival across all subjects The calculated 5-year survival is indicated for each plot
However γδ T cells are peculiar in that they do not seem to require antigen processing and major-histocompatibility-complex (MHC) presentation of peptide epitopes although some recognize MHC class Ib molecules Furthermore γδ T cells are believed to have a prominent role in recognition of lipid antigens
Imiquimod
Imiquimod (INN) is a prescription medication that acts as an immune response modifier and is used to treat genital warts superficial basal cell carcinoma and actinic keratosis Imiquimod signals to the innate arm of the immune system through the toll-like receptor 7 (TLR7)
Plasmacytoid dendritic cells (pDCs) are innate immune cells that circulate in the blood and are found in peripheral lymphoid organs They constitute lt 04 of peripheral blood mononuclear cells (PBMC) In humans these cells express the surface markers CD123 BDCA-2(CD303) and BDCA-4 (CD304) but do not express high levels of CD11c or CD14 which distinguishes them from conventional dendritic cells or monocytes respectively
TNF-related apoptosis-inducing ligand (TRAIL) is aprotein functioning as a ligand that induces the process of cell death called apoptosis TRAIL is a cytokine that is produced and secreted by most normal tissue cells It causes apoptosis primarily in tumor cells by binding to certain death receptors TRAIL has also been designated CD253 (cluster of differentiation 253)
Melanoma in situ ndash Lentigo malignaImiquimod Treatment
Mifamurtide (Mepactreg Takeda) is a drug against osteosarcoma
mainly affecting children and young adults which is lethal in about a third of cases The drug was approved in Europe in March 2009
In a phase-III clinical trial in about 800 newly diagnosed osteosarcoma patients
mifamurtide was combined with the chemotherapeutic agents doxorubicin and
methotrexate with or without cisplatin and ifosfamide The mortality could be lowered
by 30 versus chemotherapy plus placebo Six years after the treatment 78 of patients were alive Drugs in RampD 9 (2) 131ndash5 2008
Looking to the past may help planning for thefuture
Levamisole was evaluated as
an immune stimulant in a
randomized controlled study
of patients with anaplastic
gliomas who had undergone
surgical resection and who
were also treated with
radiotherapy and BCNU chemotherapy
Studies utilizing the avian sarcoma virus-induced glioma in rats also showed no
improvement in survival with levamisole stimulation as the only immune agent but
the combination of active immunization and adjuvant stimulation with bacillus
Calmette-Guerin plus levamisole was found to be therapeutically effective in this model and will be used in future pilot studies of active immunization in patients
Levamisole is a synthetic phenylimidazolthiazole that was first introduced in 1966 as an anti-helmintic agent
Current studies have been focused upon its effect on immune response and on cancer treatment
We examined the molecular mechanisms of levamisole in the activation and maturation of human
monocyte-derived dendritic cells (DC) and human T cells
Treatment of DC with levamisole increased the presentation of CD80 CD86 CD83 and human
leucocyte antigen D-related (HLA-DR) molecules on the cell membrane as well as the production of
interleukin-12 p40 and IL-10
Levamisole-treated human DC also enhanced T cell activation towards type 1 T helper immune
response by inducing interferon-γ secretion Neutralization with antibodies against Toll-like receptor
(TLR)-2 inhibited levamisole-induced production of IL-12 p40 and IL-10 suggesting a vital role for TLR-2
in signalling DC upon incubation with levamisole
In this study we showed that BALBc bone marrow-derived DC stimulated with LMS resulted in enhanced cell-
surface expression of CD80 CD86 CD40 and MHC class II as well as enhanced production of IL-12p70 TNF-α
and IL-1β Interestingly the LMS activated DCs were able to stimulate CD4(+) T cell proliferation and facilitated
Th1 differentiation by increasing the secretion of IFN-γ in an allogeneic mixed leukocyte reaction Furthermore to
confirm the in vitro data we investigated the effect of LMS on antigen-specific antibody and cytokine
production in BALBc mice Immunization with LMS plus OVA showed that anti-OVA IgG2a and IFN-γ were
increased significantly compared with OVA alone in BALBc mice
bull Aliment Pharmacol Ther 2010 Sep32(6)756-62 Meta-analysis levamisole improves the immune response to hepatitisBvaccine in dialysis patients
bull Fabrizi F1 Dixit V Messa P Martin P
bull We identified four studies involving 328 unique patients on regular dialysis Only prospective randomized clinical trials (RCTs) were included
bull Pooling of study results showed a significant increase in response rates among study (levamisole plus HBV vaccine) vs control (HBV vaccine alone) patients the pooled Odds Ratio was 2432 (95 Confidence Intervals 134 4403) P = 0002
bull Nephrology (Carlton) 2014 Jan19(1)27-31 Effectof levamisole supplementation on tetanus vaccination response rates in haemodialysis patients a randomized double-blind placebo-controlledtrial Fallahzadeh MK1 Sajjadi S Singh N Khajeh M Sagheb MM
bull At 6 months 11 out of 15 (73) patients in the levamisole group as compared with four out of 16 (25) patients in the placebo group still had protective anti-tetanus IgG levels (relative riskthinsp=thinsp293 95 CIthinsp=thinsp119 723)
bull Supplementation of Td vaccination with levamisole may enhance seroconversion against tetanus in haemodialysis patients
BCG is an attenuated (nonvirulent) form of Mycobacterium bovis cultured in 1921 by Albert Calmette and Camille Guerin at the Pasteur Institute in Lille France In the late 1920rsquos autopsy studies performed at Johns Hopkins Hospital in Baltimore Maryland showed a lower frequency of cancer in patients with tuberculosis
Attempts were made to use BCG against a variety of human cancer tumors with only limited success It wasnrsquot until the 1970rsquos however that a Canadian urologist Dr Alvaro Morales began his groundbreaking work on the use of intravesical BCG for the treatment of superficial bladder cancer Over 30 years later BCG continues to be used worldwide for the treatment of high grade noninvasive bladder cancer
Mycobacterium bovis (TEM)
We investigated whether three mycobacterial preparations currently used in the clinic (BCG and heat-killed Mycobacterium vaccae and Mycobacterium obuense) can stimulate anti-tumoureffector responses in human γδ T-cells Results show that γδ T-cells are activated by these mycobacterial preparations as indicated by upregulation of activation marker expression and proliferation
Activated γδ T-cells display enhanced effector responses as shown by upregulated granzyme B expression production of the T(H)1 cytokines IFN-γ and TNF-α and enhanced degranulation in response to susceptible and resistant tumour cells
A type of metastasis in which skin cancer spreads through a lymph vessel and begins to grow more than 2 centimeters away from the primary tumor but before it reaches the nearest lymph node
For the small uncontrolled study twenty (20) patients in advanced stages with limited life expectancy were recruited in a 2-year period Patients were classified into two groups according to the treatment to be employed Group 1 included 6 patients who refused to be treated with standard treatments and received only immunotherapy Group 2 included 14 patients treated with both immunotherapy and chemotherapyradiotherapy (CTRT) The vaccination procedure 3 intradermal doses of 05 ml each with intervals of 6 weeks between each dose Tumor fragments (about 1 g) from patients were kept in sterile PBS at minus80 degC until use For each dose about 03ndash04 g of tumor tissue were macerated in 06 ml sterile PBS
At the moment of vaccination the soluble fraction of the homogenate was mixed with formaldehyde 36 at a final concentration of 002 and 06 ml of BCG suspension 015
The survival rate upon a 5-year period was plotted for the immunotherapy only (IT) group and the combined treated (CTRTIT) group as well as for the overall survival across all subjects The calculated 5-year survival is indicated for each plot
However γδ T cells are peculiar in that they do not seem to require antigen processing and major-histocompatibility-complex (MHC) presentation of peptide epitopes although some recognize MHC class Ib molecules Furthermore γδ T cells are believed to have a prominent role in recognition of lipid antigens
Imiquimod
Imiquimod (INN) is a prescription medication that acts as an immune response modifier and is used to treat genital warts superficial basal cell carcinoma and actinic keratosis Imiquimod signals to the innate arm of the immune system through the toll-like receptor 7 (TLR7)
Plasmacytoid dendritic cells (pDCs) are innate immune cells that circulate in the blood and are found in peripheral lymphoid organs They constitute lt 04 of peripheral blood mononuclear cells (PBMC) In humans these cells express the surface markers CD123 BDCA-2(CD303) and BDCA-4 (CD304) but do not express high levels of CD11c or CD14 which distinguishes them from conventional dendritic cells or monocytes respectively
TNF-related apoptosis-inducing ligand (TRAIL) is aprotein functioning as a ligand that induces the process of cell death called apoptosis TRAIL is a cytokine that is produced and secreted by most normal tissue cells It causes apoptosis primarily in tumor cells by binding to certain death receptors TRAIL has also been designated CD253 (cluster of differentiation 253)
Melanoma in situ ndash Lentigo malignaImiquimod Treatment
Mifamurtide (Mepactreg Takeda) is a drug against osteosarcoma
mainly affecting children and young adults which is lethal in about a third of cases The drug was approved in Europe in March 2009
In a phase-III clinical trial in about 800 newly diagnosed osteosarcoma patients
mifamurtide was combined with the chemotherapeutic agents doxorubicin and
methotrexate with or without cisplatin and ifosfamide The mortality could be lowered
by 30 versus chemotherapy plus placebo Six years after the treatment 78 of patients were alive Drugs in RampD 9 (2) 131ndash5 2008
Looking to the past may help planning for thefuture
Levamisole is a synthetic phenylimidazolthiazole that was first introduced in 1966 as an anti-helmintic agent
Current studies have been focused upon its effect on immune response and on cancer treatment
We examined the molecular mechanisms of levamisole in the activation and maturation of human
monocyte-derived dendritic cells (DC) and human T cells
Treatment of DC with levamisole increased the presentation of CD80 CD86 CD83 and human
leucocyte antigen D-related (HLA-DR) molecules on the cell membrane as well as the production of
interleukin-12 p40 and IL-10
Levamisole-treated human DC also enhanced T cell activation towards type 1 T helper immune
response by inducing interferon-γ secretion Neutralization with antibodies against Toll-like receptor
(TLR)-2 inhibited levamisole-induced production of IL-12 p40 and IL-10 suggesting a vital role for TLR-2
in signalling DC upon incubation with levamisole
In this study we showed that BALBc bone marrow-derived DC stimulated with LMS resulted in enhanced cell-
surface expression of CD80 CD86 CD40 and MHC class II as well as enhanced production of IL-12p70 TNF-α
and IL-1β Interestingly the LMS activated DCs were able to stimulate CD4(+) T cell proliferation and facilitated
Th1 differentiation by increasing the secretion of IFN-γ in an allogeneic mixed leukocyte reaction Furthermore to
confirm the in vitro data we investigated the effect of LMS on antigen-specific antibody and cytokine
production in BALBc mice Immunization with LMS plus OVA showed that anti-OVA IgG2a and IFN-γ were
increased significantly compared with OVA alone in BALBc mice
bull Aliment Pharmacol Ther 2010 Sep32(6)756-62 Meta-analysis levamisole improves the immune response to hepatitisBvaccine in dialysis patients
bull Fabrizi F1 Dixit V Messa P Martin P
bull We identified four studies involving 328 unique patients on regular dialysis Only prospective randomized clinical trials (RCTs) were included
bull Pooling of study results showed a significant increase in response rates among study (levamisole plus HBV vaccine) vs control (HBV vaccine alone) patients the pooled Odds Ratio was 2432 (95 Confidence Intervals 134 4403) P = 0002
bull Nephrology (Carlton) 2014 Jan19(1)27-31 Effectof levamisole supplementation on tetanus vaccination response rates in haemodialysis patients a randomized double-blind placebo-controlledtrial Fallahzadeh MK1 Sajjadi S Singh N Khajeh M Sagheb MM
bull At 6 months 11 out of 15 (73) patients in the levamisole group as compared with four out of 16 (25) patients in the placebo group still had protective anti-tetanus IgG levels (relative riskthinsp=thinsp293 95 CIthinsp=thinsp119 723)
bull Supplementation of Td vaccination with levamisole may enhance seroconversion against tetanus in haemodialysis patients
BCG is an attenuated (nonvirulent) form of Mycobacterium bovis cultured in 1921 by Albert Calmette and Camille Guerin at the Pasteur Institute in Lille France In the late 1920rsquos autopsy studies performed at Johns Hopkins Hospital in Baltimore Maryland showed a lower frequency of cancer in patients with tuberculosis
Attempts were made to use BCG against a variety of human cancer tumors with only limited success It wasnrsquot until the 1970rsquos however that a Canadian urologist Dr Alvaro Morales began his groundbreaking work on the use of intravesical BCG for the treatment of superficial bladder cancer Over 30 years later BCG continues to be used worldwide for the treatment of high grade noninvasive bladder cancer
Mycobacterium bovis (TEM)
We investigated whether three mycobacterial preparations currently used in the clinic (BCG and heat-killed Mycobacterium vaccae and Mycobacterium obuense) can stimulate anti-tumoureffector responses in human γδ T-cells Results show that γδ T-cells are activated by these mycobacterial preparations as indicated by upregulation of activation marker expression and proliferation
Activated γδ T-cells display enhanced effector responses as shown by upregulated granzyme B expression production of the T(H)1 cytokines IFN-γ and TNF-α and enhanced degranulation in response to susceptible and resistant tumour cells
A type of metastasis in which skin cancer spreads through a lymph vessel and begins to grow more than 2 centimeters away from the primary tumor but before it reaches the nearest lymph node
For the small uncontrolled study twenty (20) patients in advanced stages with limited life expectancy were recruited in a 2-year period Patients were classified into two groups according to the treatment to be employed Group 1 included 6 patients who refused to be treated with standard treatments and received only immunotherapy Group 2 included 14 patients treated with both immunotherapy and chemotherapyradiotherapy (CTRT) The vaccination procedure 3 intradermal doses of 05 ml each with intervals of 6 weeks between each dose Tumor fragments (about 1 g) from patients were kept in sterile PBS at minus80 degC until use For each dose about 03ndash04 g of tumor tissue were macerated in 06 ml sterile PBS
At the moment of vaccination the soluble fraction of the homogenate was mixed with formaldehyde 36 at a final concentration of 002 and 06 ml of BCG suspension 015
The survival rate upon a 5-year period was plotted for the immunotherapy only (IT) group and the combined treated (CTRTIT) group as well as for the overall survival across all subjects The calculated 5-year survival is indicated for each plot
However γδ T cells are peculiar in that they do not seem to require antigen processing and major-histocompatibility-complex (MHC) presentation of peptide epitopes although some recognize MHC class Ib molecules Furthermore γδ T cells are believed to have a prominent role in recognition of lipid antigens
Imiquimod
Imiquimod (INN) is a prescription medication that acts as an immune response modifier and is used to treat genital warts superficial basal cell carcinoma and actinic keratosis Imiquimod signals to the innate arm of the immune system through the toll-like receptor 7 (TLR7)
Plasmacytoid dendritic cells (pDCs) are innate immune cells that circulate in the blood and are found in peripheral lymphoid organs They constitute lt 04 of peripheral blood mononuclear cells (PBMC) In humans these cells express the surface markers CD123 BDCA-2(CD303) and BDCA-4 (CD304) but do not express high levels of CD11c or CD14 which distinguishes them from conventional dendritic cells or monocytes respectively
TNF-related apoptosis-inducing ligand (TRAIL) is aprotein functioning as a ligand that induces the process of cell death called apoptosis TRAIL is a cytokine that is produced and secreted by most normal tissue cells It causes apoptosis primarily in tumor cells by binding to certain death receptors TRAIL has also been designated CD253 (cluster of differentiation 253)
Melanoma in situ ndash Lentigo malignaImiquimod Treatment
Mifamurtide (Mepactreg Takeda) is a drug against osteosarcoma
mainly affecting children and young adults which is lethal in about a third of cases The drug was approved in Europe in March 2009
In a phase-III clinical trial in about 800 newly diagnosed osteosarcoma patients
mifamurtide was combined with the chemotherapeutic agents doxorubicin and
methotrexate with or without cisplatin and ifosfamide The mortality could be lowered
by 30 versus chemotherapy plus placebo Six years after the treatment 78 of patients were alive Drugs in RampD 9 (2) 131ndash5 2008
Looking to the past may help planning for thefuture
In this study we showed that BALBc bone marrow-derived DC stimulated with LMS resulted in enhanced cell-
surface expression of CD80 CD86 CD40 and MHC class II as well as enhanced production of IL-12p70 TNF-α
and IL-1β Interestingly the LMS activated DCs were able to stimulate CD4(+) T cell proliferation and facilitated
Th1 differentiation by increasing the secretion of IFN-γ in an allogeneic mixed leukocyte reaction Furthermore to
confirm the in vitro data we investigated the effect of LMS on antigen-specific antibody and cytokine
production in BALBc mice Immunization with LMS plus OVA showed that anti-OVA IgG2a and IFN-γ were
increased significantly compared with OVA alone in BALBc mice
bull Aliment Pharmacol Ther 2010 Sep32(6)756-62 Meta-analysis levamisole improves the immune response to hepatitisBvaccine in dialysis patients
bull Fabrizi F1 Dixit V Messa P Martin P
bull We identified four studies involving 328 unique patients on regular dialysis Only prospective randomized clinical trials (RCTs) were included
bull Pooling of study results showed a significant increase in response rates among study (levamisole plus HBV vaccine) vs control (HBV vaccine alone) patients the pooled Odds Ratio was 2432 (95 Confidence Intervals 134 4403) P = 0002
bull Nephrology (Carlton) 2014 Jan19(1)27-31 Effectof levamisole supplementation on tetanus vaccination response rates in haemodialysis patients a randomized double-blind placebo-controlledtrial Fallahzadeh MK1 Sajjadi S Singh N Khajeh M Sagheb MM
bull At 6 months 11 out of 15 (73) patients in the levamisole group as compared with four out of 16 (25) patients in the placebo group still had protective anti-tetanus IgG levels (relative riskthinsp=thinsp293 95 CIthinsp=thinsp119 723)
bull Supplementation of Td vaccination with levamisole may enhance seroconversion against tetanus in haemodialysis patients
BCG is an attenuated (nonvirulent) form of Mycobacterium bovis cultured in 1921 by Albert Calmette and Camille Guerin at the Pasteur Institute in Lille France In the late 1920rsquos autopsy studies performed at Johns Hopkins Hospital in Baltimore Maryland showed a lower frequency of cancer in patients with tuberculosis
Attempts were made to use BCG against a variety of human cancer tumors with only limited success It wasnrsquot until the 1970rsquos however that a Canadian urologist Dr Alvaro Morales began his groundbreaking work on the use of intravesical BCG for the treatment of superficial bladder cancer Over 30 years later BCG continues to be used worldwide for the treatment of high grade noninvasive bladder cancer
Mycobacterium bovis (TEM)
We investigated whether three mycobacterial preparations currently used in the clinic (BCG and heat-killed Mycobacterium vaccae and Mycobacterium obuense) can stimulate anti-tumoureffector responses in human γδ T-cells Results show that γδ T-cells are activated by these mycobacterial preparations as indicated by upregulation of activation marker expression and proliferation
Activated γδ T-cells display enhanced effector responses as shown by upregulated granzyme B expression production of the T(H)1 cytokines IFN-γ and TNF-α and enhanced degranulation in response to susceptible and resistant tumour cells
A type of metastasis in which skin cancer spreads through a lymph vessel and begins to grow more than 2 centimeters away from the primary tumor but before it reaches the nearest lymph node
For the small uncontrolled study twenty (20) patients in advanced stages with limited life expectancy were recruited in a 2-year period Patients were classified into two groups according to the treatment to be employed Group 1 included 6 patients who refused to be treated with standard treatments and received only immunotherapy Group 2 included 14 patients treated with both immunotherapy and chemotherapyradiotherapy (CTRT) The vaccination procedure 3 intradermal doses of 05 ml each with intervals of 6 weeks between each dose Tumor fragments (about 1 g) from patients were kept in sterile PBS at minus80 degC until use For each dose about 03ndash04 g of tumor tissue were macerated in 06 ml sterile PBS
At the moment of vaccination the soluble fraction of the homogenate was mixed with formaldehyde 36 at a final concentration of 002 and 06 ml of BCG suspension 015
The survival rate upon a 5-year period was plotted for the immunotherapy only (IT) group and the combined treated (CTRTIT) group as well as for the overall survival across all subjects The calculated 5-year survival is indicated for each plot
However γδ T cells are peculiar in that they do not seem to require antigen processing and major-histocompatibility-complex (MHC) presentation of peptide epitopes although some recognize MHC class Ib molecules Furthermore γδ T cells are believed to have a prominent role in recognition of lipid antigens
Imiquimod
Imiquimod (INN) is a prescription medication that acts as an immune response modifier and is used to treat genital warts superficial basal cell carcinoma and actinic keratosis Imiquimod signals to the innate arm of the immune system through the toll-like receptor 7 (TLR7)
Plasmacytoid dendritic cells (pDCs) are innate immune cells that circulate in the blood and are found in peripheral lymphoid organs They constitute lt 04 of peripheral blood mononuclear cells (PBMC) In humans these cells express the surface markers CD123 BDCA-2(CD303) and BDCA-4 (CD304) but do not express high levels of CD11c or CD14 which distinguishes them from conventional dendritic cells or monocytes respectively
TNF-related apoptosis-inducing ligand (TRAIL) is aprotein functioning as a ligand that induces the process of cell death called apoptosis TRAIL is a cytokine that is produced and secreted by most normal tissue cells It causes apoptosis primarily in tumor cells by binding to certain death receptors TRAIL has also been designated CD253 (cluster of differentiation 253)
Melanoma in situ ndash Lentigo malignaImiquimod Treatment
Mifamurtide (Mepactreg Takeda) is a drug against osteosarcoma
mainly affecting children and young adults which is lethal in about a third of cases The drug was approved in Europe in March 2009
In a phase-III clinical trial in about 800 newly diagnosed osteosarcoma patients
mifamurtide was combined with the chemotherapeutic agents doxorubicin and
methotrexate with or without cisplatin and ifosfamide The mortality could be lowered
by 30 versus chemotherapy plus placebo Six years after the treatment 78 of patients were alive Drugs in RampD 9 (2) 131ndash5 2008
Looking to the past may help planning for thefuture
bull Aliment Pharmacol Ther 2010 Sep32(6)756-62 Meta-analysis levamisole improves the immune response to hepatitisBvaccine in dialysis patients
bull Fabrizi F1 Dixit V Messa P Martin P
bull We identified four studies involving 328 unique patients on regular dialysis Only prospective randomized clinical trials (RCTs) were included
bull Pooling of study results showed a significant increase in response rates among study (levamisole plus HBV vaccine) vs control (HBV vaccine alone) patients the pooled Odds Ratio was 2432 (95 Confidence Intervals 134 4403) P = 0002
bull Nephrology (Carlton) 2014 Jan19(1)27-31 Effectof levamisole supplementation on tetanus vaccination response rates in haemodialysis patients a randomized double-blind placebo-controlledtrial Fallahzadeh MK1 Sajjadi S Singh N Khajeh M Sagheb MM
bull At 6 months 11 out of 15 (73) patients in the levamisole group as compared with four out of 16 (25) patients in the placebo group still had protective anti-tetanus IgG levels (relative riskthinsp=thinsp293 95 CIthinsp=thinsp119 723)
bull Supplementation of Td vaccination with levamisole may enhance seroconversion against tetanus in haemodialysis patients
BCG is an attenuated (nonvirulent) form of Mycobacterium bovis cultured in 1921 by Albert Calmette and Camille Guerin at the Pasteur Institute in Lille France In the late 1920rsquos autopsy studies performed at Johns Hopkins Hospital in Baltimore Maryland showed a lower frequency of cancer in patients with tuberculosis
Attempts were made to use BCG against a variety of human cancer tumors with only limited success It wasnrsquot until the 1970rsquos however that a Canadian urologist Dr Alvaro Morales began his groundbreaking work on the use of intravesical BCG for the treatment of superficial bladder cancer Over 30 years later BCG continues to be used worldwide for the treatment of high grade noninvasive bladder cancer
Mycobacterium bovis (TEM)
We investigated whether three mycobacterial preparations currently used in the clinic (BCG and heat-killed Mycobacterium vaccae and Mycobacterium obuense) can stimulate anti-tumoureffector responses in human γδ T-cells Results show that γδ T-cells are activated by these mycobacterial preparations as indicated by upregulation of activation marker expression and proliferation
Activated γδ T-cells display enhanced effector responses as shown by upregulated granzyme B expression production of the T(H)1 cytokines IFN-γ and TNF-α and enhanced degranulation in response to susceptible and resistant tumour cells
A type of metastasis in which skin cancer spreads through a lymph vessel and begins to grow more than 2 centimeters away from the primary tumor but before it reaches the nearest lymph node
For the small uncontrolled study twenty (20) patients in advanced stages with limited life expectancy were recruited in a 2-year period Patients were classified into two groups according to the treatment to be employed Group 1 included 6 patients who refused to be treated with standard treatments and received only immunotherapy Group 2 included 14 patients treated with both immunotherapy and chemotherapyradiotherapy (CTRT) The vaccination procedure 3 intradermal doses of 05 ml each with intervals of 6 weeks between each dose Tumor fragments (about 1 g) from patients were kept in sterile PBS at minus80 degC until use For each dose about 03ndash04 g of tumor tissue were macerated in 06 ml sterile PBS
At the moment of vaccination the soluble fraction of the homogenate was mixed with formaldehyde 36 at a final concentration of 002 and 06 ml of BCG suspension 015
The survival rate upon a 5-year period was plotted for the immunotherapy only (IT) group and the combined treated (CTRTIT) group as well as for the overall survival across all subjects The calculated 5-year survival is indicated for each plot
However γδ T cells are peculiar in that they do not seem to require antigen processing and major-histocompatibility-complex (MHC) presentation of peptide epitopes although some recognize MHC class Ib molecules Furthermore γδ T cells are believed to have a prominent role in recognition of lipid antigens
Imiquimod
Imiquimod (INN) is a prescription medication that acts as an immune response modifier and is used to treat genital warts superficial basal cell carcinoma and actinic keratosis Imiquimod signals to the innate arm of the immune system through the toll-like receptor 7 (TLR7)
Plasmacytoid dendritic cells (pDCs) are innate immune cells that circulate in the blood and are found in peripheral lymphoid organs They constitute lt 04 of peripheral blood mononuclear cells (PBMC) In humans these cells express the surface markers CD123 BDCA-2(CD303) and BDCA-4 (CD304) but do not express high levels of CD11c or CD14 which distinguishes them from conventional dendritic cells or monocytes respectively
TNF-related apoptosis-inducing ligand (TRAIL) is aprotein functioning as a ligand that induces the process of cell death called apoptosis TRAIL is a cytokine that is produced and secreted by most normal tissue cells It causes apoptosis primarily in tumor cells by binding to certain death receptors TRAIL has also been designated CD253 (cluster of differentiation 253)
Melanoma in situ ndash Lentigo malignaImiquimod Treatment
Mifamurtide (Mepactreg Takeda) is a drug against osteosarcoma
mainly affecting children and young adults which is lethal in about a third of cases The drug was approved in Europe in March 2009
In a phase-III clinical trial in about 800 newly diagnosed osteosarcoma patients
mifamurtide was combined with the chemotherapeutic agents doxorubicin and
methotrexate with or without cisplatin and ifosfamide The mortality could be lowered
by 30 versus chemotherapy plus placebo Six years after the treatment 78 of patients were alive Drugs in RampD 9 (2) 131ndash5 2008
Looking to the past may help planning for thefuture
bull Nephrology (Carlton) 2014 Jan19(1)27-31 Effectof levamisole supplementation on tetanus vaccination response rates in haemodialysis patients a randomized double-blind placebo-controlledtrial Fallahzadeh MK1 Sajjadi S Singh N Khajeh M Sagheb MM
bull At 6 months 11 out of 15 (73) patients in the levamisole group as compared with four out of 16 (25) patients in the placebo group still had protective anti-tetanus IgG levels (relative riskthinsp=thinsp293 95 CIthinsp=thinsp119 723)
bull Supplementation of Td vaccination with levamisole may enhance seroconversion against tetanus in haemodialysis patients
BCG is an attenuated (nonvirulent) form of Mycobacterium bovis cultured in 1921 by Albert Calmette and Camille Guerin at the Pasteur Institute in Lille France In the late 1920rsquos autopsy studies performed at Johns Hopkins Hospital in Baltimore Maryland showed a lower frequency of cancer in patients with tuberculosis
Attempts were made to use BCG against a variety of human cancer tumors with only limited success It wasnrsquot until the 1970rsquos however that a Canadian urologist Dr Alvaro Morales began his groundbreaking work on the use of intravesical BCG for the treatment of superficial bladder cancer Over 30 years later BCG continues to be used worldwide for the treatment of high grade noninvasive bladder cancer
Mycobacterium bovis (TEM)
We investigated whether three mycobacterial preparations currently used in the clinic (BCG and heat-killed Mycobacterium vaccae and Mycobacterium obuense) can stimulate anti-tumoureffector responses in human γδ T-cells Results show that γδ T-cells are activated by these mycobacterial preparations as indicated by upregulation of activation marker expression and proliferation
Activated γδ T-cells display enhanced effector responses as shown by upregulated granzyme B expression production of the T(H)1 cytokines IFN-γ and TNF-α and enhanced degranulation in response to susceptible and resistant tumour cells
A type of metastasis in which skin cancer spreads through a lymph vessel and begins to grow more than 2 centimeters away from the primary tumor but before it reaches the nearest lymph node
For the small uncontrolled study twenty (20) patients in advanced stages with limited life expectancy were recruited in a 2-year period Patients were classified into two groups according to the treatment to be employed Group 1 included 6 patients who refused to be treated with standard treatments and received only immunotherapy Group 2 included 14 patients treated with both immunotherapy and chemotherapyradiotherapy (CTRT) The vaccination procedure 3 intradermal doses of 05 ml each with intervals of 6 weeks between each dose Tumor fragments (about 1 g) from patients were kept in sterile PBS at minus80 degC until use For each dose about 03ndash04 g of tumor tissue were macerated in 06 ml sterile PBS
At the moment of vaccination the soluble fraction of the homogenate was mixed with formaldehyde 36 at a final concentration of 002 and 06 ml of BCG suspension 015
The survival rate upon a 5-year period was plotted for the immunotherapy only (IT) group and the combined treated (CTRTIT) group as well as for the overall survival across all subjects The calculated 5-year survival is indicated for each plot
However γδ T cells are peculiar in that they do not seem to require antigen processing and major-histocompatibility-complex (MHC) presentation of peptide epitopes although some recognize MHC class Ib molecules Furthermore γδ T cells are believed to have a prominent role in recognition of lipid antigens
Imiquimod
Imiquimod (INN) is a prescription medication that acts as an immune response modifier and is used to treat genital warts superficial basal cell carcinoma and actinic keratosis Imiquimod signals to the innate arm of the immune system through the toll-like receptor 7 (TLR7)
Plasmacytoid dendritic cells (pDCs) are innate immune cells that circulate in the blood and are found in peripheral lymphoid organs They constitute lt 04 of peripheral blood mononuclear cells (PBMC) In humans these cells express the surface markers CD123 BDCA-2(CD303) and BDCA-4 (CD304) but do not express high levels of CD11c or CD14 which distinguishes them from conventional dendritic cells or monocytes respectively
TNF-related apoptosis-inducing ligand (TRAIL) is aprotein functioning as a ligand that induces the process of cell death called apoptosis TRAIL is a cytokine that is produced and secreted by most normal tissue cells It causes apoptosis primarily in tumor cells by binding to certain death receptors TRAIL has also been designated CD253 (cluster of differentiation 253)
Melanoma in situ ndash Lentigo malignaImiquimod Treatment
Mifamurtide (Mepactreg Takeda) is a drug against osteosarcoma
mainly affecting children and young adults which is lethal in about a third of cases The drug was approved in Europe in March 2009
In a phase-III clinical trial in about 800 newly diagnosed osteosarcoma patients
mifamurtide was combined with the chemotherapeutic agents doxorubicin and
methotrexate with or without cisplatin and ifosfamide The mortality could be lowered
by 30 versus chemotherapy plus placebo Six years after the treatment 78 of patients were alive Drugs in RampD 9 (2) 131ndash5 2008
Looking to the past may help planning for thefuture
BCG is an attenuated (nonvirulent) form of Mycobacterium bovis cultured in 1921 by Albert Calmette and Camille Guerin at the Pasteur Institute in Lille France In the late 1920rsquos autopsy studies performed at Johns Hopkins Hospital in Baltimore Maryland showed a lower frequency of cancer in patients with tuberculosis
Attempts were made to use BCG against a variety of human cancer tumors with only limited success It wasnrsquot until the 1970rsquos however that a Canadian urologist Dr Alvaro Morales began his groundbreaking work on the use of intravesical BCG for the treatment of superficial bladder cancer Over 30 years later BCG continues to be used worldwide for the treatment of high grade noninvasive bladder cancer
Mycobacterium bovis (TEM)
We investigated whether three mycobacterial preparations currently used in the clinic (BCG and heat-killed Mycobacterium vaccae and Mycobacterium obuense) can stimulate anti-tumoureffector responses in human γδ T-cells Results show that γδ T-cells are activated by these mycobacterial preparations as indicated by upregulation of activation marker expression and proliferation
Activated γδ T-cells display enhanced effector responses as shown by upregulated granzyme B expression production of the T(H)1 cytokines IFN-γ and TNF-α and enhanced degranulation in response to susceptible and resistant tumour cells
A type of metastasis in which skin cancer spreads through a lymph vessel and begins to grow more than 2 centimeters away from the primary tumor but before it reaches the nearest lymph node
For the small uncontrolled study twenty (20) patients in advanced stages with limited life expectancy were recruited in a 2-year period Patients were classified into two groups according to the treatment to be employed Group 1 included 6 patients who refused to be treated with standard treatments and received only immunotherapy Group 2 included 14 patients treated with both immunotherapy and chemotherapyradiotherapy (CTRT) The vaccination procedure 3 intradermal doses of 05 ml each with intervals of 6 weeks between each dose Tumor fragments (about 1 g) from patients were kept in sterile PBS at minus80 degC until use For each dose about 03ndash04 g of tumor tissue were macerated in 06 ml sterile PBS
At the moment of vaccination the soluble fraction of the homogenate was mixed with formaldehyde 36 at a final concentration of 002 and 06 ml of BCG suspension 015
The survival rate upon a 5-year period was plotted for the immunotherapy only (IT) group and the combined treated (CTRTIT) group as well as for the overall survival across all subjects The calculated 5-year survival is indicated for each plot
However γδ T cells are peculiar in that they do not seem to require antigen processing and major-histocompatibility-complex (MHC) presentation of peptide epitopes although some recognize MHC class Ib molecules Furthermore γδ T cells are believed to have a prominent role in recognition of lipid antigens
Imiquimod
Imiquimod (INN) is a prescription medication that acts as an immune response modifier and is used to treat genital warts superficial basal cell carcinoma and actinic keratosis Imiquimod signals to the innate arm of the immune system through the toll-like receptor 7 (TLR7)
Plasmacytoid dendritic cells (pDCs) are innate immune cells that circulate in the blood and are found in peripheral lymphoid organs They constitute lt 04 of peripheral blood mononuclear cells (PBMC) In humans these cells express the surface markers CD123 BDCA-2(CD303) and BDCA-4 (CD304) but do not express high levels of CD11c or CD14 which distinguishes them from conventional dendritic cells or monocytes respectively
TNF-related apoptosis-inducing ligand (TRAIL) is aprotein functioning as a ligand that induces the process of cell death called apoptosis TRAIL is a cytokine that is produced and secreted by most normal tissue cells It causes apoptosis primarily in tumor cells by binding to certain death receptors TRAIL has also been designated CD253 (cluster of differentiation 253)
Melanoma in situ ndash Lentigo malignaImiquimod Treatment
Mifamurtide (Mepactreg Takeda) is a drug against osteosarcoma
mainly affecting children and young adults which is lethal in about a third of cases The drug was approved in Europe in March 2009
In a phase-III clinical trial in about 800 newly diagnosed osteosarcoma patients
mifamurtide was combined with the chemotherapeutic agents doxorubicin and
methotrexate with or without cisplatin and ifosfamide The mortality could be lowered
by 30 versus chemotherapy plus placebo Six years after the treatment 78 of patients were alive Drugs in RampD 9 (2) 131ndash5 2008
Looking to the past may help planning for thefuture
Mycobacterium bovis (TEM)
We investigated whether three mycobacterial preparations currently used in the clinic (BCG and heat-killed Mycobacterium vaccae and Mycobacterium obuense) can stimulate anti-tumoureffector responses in human γδ T-cells Results show that γδ T-cells are activated by these mycobacterial preparations as indicated by upregulation of activation marker expression and proliferation
Activated γδ T-cells display enhanced effector responses as shown by upregulated granzyme B expression production of the T(H)1 cytokines IFN-γ and TNF-α and enhanced degranulation in response to susceptible and resistant tumour cells
A type of metastasis in which skin cancer spreads through a lymph vessel and begins to grow more than 2 centimeters away from the primary tumor but before it reaches the nearest lymph node
For the small uncontrolled study twenty (20) patients in advanced stages with limited life expectancy were recruited in a 2-year period Patients were classified into two groups according to the treatment to be employed Group 1 included 6 patients who refused to be treated with standard treatments and received only immunotherapy Group 2 included 14 patients treated with both immunotherapy and chemotherapyradiotherapy (CTRT) The vaccination procedure 3 intradermal doses of 05 ml each with intervals of 6 weeks between each dose Tumor fragments (about 1 g) from patients were kept in sterile PBS at minus80 degC until use For each dose about 03ndash04 g of tumor tissue were macerated in 06 ml sterile PBS
At the moment of vaccination the soluble fraction of the homogenate was mixed with formaldehyde 36 at a final concentration of 002 and 06 ml of BCG suspension 015
The survival rate upon a 5-year period was plotted for the immunotherapy only (IT) group and the combined treated (CTRTIT) group as well as for the overall survival across all subjects The calculated 5-year survival is indicated for each plot
However γδ T cells are peculiar in that they do not seem to require antigen processing and major-histocompatibility-complex (MHC) presentation of peptide epitopes although some recognize MHC class Ib molecules Furthermore γδ T cells are believed to have a prominent role in recognition of lipid antigens
Imiquimod
Imiquimod (INN) is a prescription medication that acts as an immune response modifier and is used to treat genital warts superficial basal cell carcinoma and actinic keratosis Imiquimod signals to the innate arm of the immune system through the toll-like receptor 7 (TLR7)
Plasmacytoid dendritic cells (pDCs) are innate immune cells that circulate in the blood and are found in peripheral lymphoid organs They constitute lt 04 of peripheral blood mononuclear cells (PBMC) In humans these cells express the surface markers CD123 BDCA-2(CD303) and BDCA-4 (CD304) but do not express high levels of CD11c or CD14 which distinguishes them from conventional dendritic cells or monocytes respectively
TNF-related apoptosis-inducing ligand (TRAIL) is aprotein functioning as a ligand that induces the process of cell death called apoptosis TRAIL is a cytokine that is produced and secreted by most normal tissue cells It causes apoptosis primarily in tumor cells by binding to certain death receptors TRAIL has also been designated CD253 (cluster of differentiation 253)
Melanoma in situ ndash Lentigo malignaImiquimod Treatment
Mifamurtide (Mepactreg Takeda) is a drug against osteosarcoma
mainly affecting children and young adults which is lethal in about a third of cases The drug was approved in Europe in March 2009
In a phase-III clinical trial in about 800 newly diagnosed osteosarcoma patients
mifamurtide was combined with the chemotherapeutic agents doxorubicin and
methotrexate with or without cisplatin and ifosfamide The mortality could be lowered
by 30 versus chemotherapy plus placebo Six years after the treatment 78 of patients were alive Drugs in RampD 9 (2) 131ndash5 2008
Looking to the past may help planning for thefuture
We investigated whether three mycobacterial preparations currently used in the clinic (BCG and heat-killed Mycobacterium vaccae and Mycobacterium obuense) can stimulate anti-tumoureffector responses in human γδ T-cells Results show that γδ T-cells are activated by these mycobacterial preparations as indicated by upregulation of activation marker expression and proliferation
Activated γδ T-cells display enhanced effector responses as shown by upregulated granzyme B expression production of the T(H)1 cytokines IFN-γ and TNF-α and enhanced degranulation in response to susceptible and resistant tumour cells
A type of metastasis in which skin cancer spreads through a lymph vessel and begins to grow more than 2 centimeters away from the primary tumor but before it reaches the nearest lymph node
For the small uncontrolled study twenty (20) patients in advanced stages with limited life expectancy were recruited in a 2-year period Patients were classified into two groups according to the treatment to be employed Group 1 included 6 patients who refused to be treated with standard treatments and received only immunotherapy Group 2 included 14 patients treated with both immunotherapy and chemotherapyradiotherapy (CTRT) The vaccination procedure 3 intradermal doses of 05 ml each with intervals of 6 weeks between each dose Tumor fragments (about 1 g) from patients were kept in sterile PBS at minus80 degC until use For each dose about 03ndash04 g of tumor tissue were macerated in 06 ml sterile PBS
At the moment of vaccination the soluble fraction of the homogenate was mixed with formaldehyde 36 at a final concentration of 002 and 06 ml of BCG suspension 015
The survival rate upon a 5-year period was plotted for the immunotherapy only (IT) group and the combined treated (CTRTIT) group as well as for the overall survival across all subjects The calculated 5-year survival is indicated for each plot
However γδ T cells are peculiar in that they do not seem to require antigen processing and major-histocompatibility-complex (MHC) presentation of peptide epitopes although some recognize MHC class Ib molecules Furthermore γδ T cells are believed to have a prominent role in recognition of lipid antigens
Imiquimod
Imiquimod (INN) is a prescription medication that acts as an immune response modifier and is used to treat genital warts superficial basal cell carcinoma and actinic keratosis Imiquimod signals to the innate arm of the immune system through the toll-like receptor 7 (TLR7)
Plasmacytoid dendritic cells (pDCs) are innate immune cells that circulate in the blood and are found in peripheral lymphoid organs They constitute lt 04 of peripheral blood mononuclear cells (PBMC) In humans these cells express the surface markers CD123 BDCA-2(CD303) and BDCA-4 (CD304) but do not express high levels of CD11c or CD14 which distinguishes them from conventional dendritic cells or monocytes respectively
TNF-related apoptosis-inducing ligand (TRAIL) is aprotein functioning as a ligand that induces the process of cell death called apoptosis TRAIL is a cytokine that is produced and secreted by most normal tissue cells It causes apoptosis primarily in tumor cells by binding to certain death receptors TRAIL has also been designated CD253 (cluster of differentiation 253)
Melanoma in situ ndash Lentigo malignaImiquimod Treatment
Mifamurtide (Mepactreg Takeda) is a drug against osteosarcoma
mainly affecting children and young adults which is lethal in about a third of cases The drug was approved in Europe in March 2009
In a phase-III clinical trial in about 800 newly diagnosed osteosarcoma patients
mifamurtide was combined with the chemotherapeutic agents doxorubicin and
methotrexate with or without cisplatin and ifosfamide The mortality could be lowered
by 30 versus chemotherapy plus placebo Six years after the treatment 78 of patients were alive Drugs in RampD 9 (2) 131ndash5 2008
Looking to the past may help planning for thefuture
A type of metastasis in which skin cancer spreads through a lymph vessel and begins to grow more than 2 centimeters away from the primary tumor but before it reaches the nearest lymph node
For the small uncontrolled study twenty (20) patients in advanced stages with limited life expectancy were recruited in a 2-year period Patients were classified into two groups according to the treatment to be employed Group 1 included 6 patients who refused to be treated with standard treatments and received only immunotherapy Group 2 included 14 patients treated with both immunotherapy and chemotherapyradiotherapy (CTRT) The vaccination procedure 3 intradermal doses of 05 ml each with intervals of 6 weeks between each dose Tumor fragments (about 1 g) from patients were kept in sterile PBS at minus80 degC until use For each dose about 03ndash04 g of tumor tissue were macerated in 06 ml sterile PBS
At the moment of vaccination the soluble fraction of the homogenate was mixed with formaldehyde 36 at a final concentration of 002 and 06 ml of BCG suspension 015
The survival rate upon a 5-year period was plotted for the immunotherapy only (IT) group and the combined treated (CTRTIT) group as well as for the overall survival across all subjects The calculated 5-year survival is indicated for each plot
However γδ T cells are peculiar in that they do not seem to require antigen processing and major-histocompatibility-complex (MHC) presentation of peptide epitopes although some recognize MHC class Ib molecules Furthermore γδ T cells are believed to have a prominent role in recognition of lipid antigens
Imiquimod
Imiquimod (INN) is a prescription medication that acts as an immune response modifier and is used to treat genital warts superficial basal cell carcinoma and actinic keratosis Imiquimod signals to the innate arm of the immune system through the toll-like receptor 7 (TLR7)
Plasmacytoid dendritic cells (pDCs) are innate immune cells that circulate in the blood and are found in peripheral lymphoid organs They constitute lt 04 of peripheral blood mononuclear cells (PBMC) In humans these cells express the surface markers CD123 BDCA-2(CD303) and BDCA-4 (CD304) but do not express high levels of CD11c or CD14 which distinguishes them from conventional dendritic cells or monocytes respectively
TNF-related apoptosis-inducing ligand (TRAIL) is aprotein functioning as a ligand that induces the process of cell death called apoptosis TRAIL is a cytokine that is produced and secreted by most normal tissue cells It causes apoptosis primarily in tumor cells by binding to certain death receptors TRAIL has also been designated CD253 (cluster of differentiation 253)
Melanoma in situ ndash Lentigo malignaImiquimod Treatment
Mifamurtide (Mepactreg Takeda) is a drug against osteosarcoma
mainly affecting children and young adults which is lethal in about a third of cases The drug was approved in Europe in March 2009
In a phase-III clinical trial in about 800 newly diagnosed osteosarcoma patients
mifamurtide was combined with the chemotherapeutic agents doxorubicin and
methotrexate with or without cisplatin and ifosfamide The mortality could be lowered
by 30 versus chemotherapy plus placebo Six years after the treatment 78 of patients were alive Drugs in RampD 9 (2) 131ndash5 2008
Looking to the past may help planning for thefuture
For the small uncontrolled study twenty (20) patients in advanced stages with limited life expectancy were recruited in a 2-year period Patients were classified into two groups according to the treatment to be employed Group 1 included 6 patients who refused to be treated with standard treatments and received only immunotherapy Group 2 included 14 patients treated with both immunotherapy and chemotherapyradiotherapy (CTRT) The vaccination procedure 3 intradermal doses of 05 ml each with intervals of 6 weeks between each dose Tumor fragments (about 1 g) from patients were kept in sterile PBS at minus80 degC until use For each dose about 03ndash04 g of tumor tissue were macerated in 06 ml sterile PBS
At the moment of vaccination the soluble fraction of the homogenate was mixed with formaldehyde 36 at a final concentration of 002 and 06 ml of BCG suspension 015
The survival rate upon a 5-year period was plotted for the immunotherapy only (IT) group and the combined treated (CTRTIT) group as well as for the overall survival across all subjects The calculated 5-year survival is indicated for each plot
However γδ T cells are peculiar in that they do not seem to require antigen processing and major-histocompatibility-complex (MHC) presentation of peptide epitopes although some recognize MHC class Ib molecules Furthermore γδ T cells are believed to have a prominent role in recognition of lipid antigens
Imiquimod
Imiquimod (INN) is a prescription medication that acts as an immune response modifier and is used to treat genital warts superficial basal cell carcinoma and actinic keratosis Imiquimod signals to the innate arm of the immune system through the toll-like receptor 7 (TLR7)
Plasmacytoid dendritic cells (pDCs) are innate immune cells that circulate in the blood and are found in peripheral lymphoid organs They constitute lt 04 of peripheral blood mononuclear cells (PBMC) In humans these cells express the surface markers CD123 BDCA-2(CD303) and BDCA-4 (CD304) but do not express high levels of CD11c or CD14 which distinguishes them from conventional dendritic cells or monocytes respectively
TNF-related apoptosis-inducing ligand (TRAIL) is aprotein functioning as a ligand that induces the process of cell death called apoptosis TRAIL is a cytokine that is produced and secreted by most normal tissue cells It causes apoptosis primarily in tumor cells by binding to certain death receptors TRAIL has also been designated CD253 (cluster of differentiation 253)
Melanoma in situ ndash Lentigo malignaImiquimod Treatment
Mifamurtide (Mepactreg Takeda) is a drug against osteosarcoma
mainly affecting children and young adults which is lethal in about a third of cases The drug was approved in Europe in March 2009
In a phase-III clinical trial in about 800 newly diagnosed osteosarcoma patients
mifamurtide was combined with the chemotherapeutic agents doxorubicin and
methotrexate with or without cisplatin and ifosfamide The mortality could be lowered
by 30 versus chemotherapy plus placebo Six years after the treatment 78 of patients were alive Drugs in RampD 9 (2) 131ndash5 2008
Looking to the past may help planning for thefuture
The survival rate upon a 5-year period was plotted for the immunotherapy only (IT) group and the combined treated (CTRTIT) group as well as for the overall survival across all subjects The calculated 5-year survival is indicated for each plot
However γδ T cells are peculiar in that they do not seem to require antigen processing and major-histocompatibility-complex (MHC) presentation of peptide epitopes although some recognize MHC class Ib molecules Furthermore γδ T cells are believed to have a prominent role in recognition of lipid antigens
Imiquimod
Imiquimod (INN) is a prescription medication that acts as an immune response modifier and is used to treat genital warts superficial basal cell carcinoma and actinic keratosis Imiquimod signals to the innate arm of the immune system through the toll-like receptor 7 (TLR7)
Plasmacytoid dendritic cells (pDCs) are innate immune cells that circulate in the blood and are found in peripheral lymphoid organs They constitute lt 04 of peripheral blood mononuclear cells (PBMC) In humans these cells express the surface markers CD123 BDCA-2(CD303) and BDCA-4 (CD304) but do not express high levels of CD11c or CD14 which distinguishes them from conventional dendritic cells or monocytes respectively
TNF-related apoptosis-inducing ligand (TRAIL) is aprotein functioning as a ligand that induces the process of cell death called apoptosis TRAIL is a cytokine that is produced and secreted by most normal tissue cells It causes apoptosis primarily in tumor cells by binding to certain death receptors TRAIL has also been designated CD253 (cluster of differentiation 253)
Melanoma in situ ndash Lentigo malignaImiquimod Treatment
Mifamurtide (Mepactreg Takeda) is a drug against osteosarcoma
mainly affecting children and young adults which is lethal in about a third of cases The drug was approved in Europe in March 2009
In a phase-III clinical trial in about 800 newly diagnosed osteosarcoma patients
mifamurtide was combined with the chemotherapeutic agents doxorubicin and
methotrexate with or without cisplatin and ifosfamide The mortality could be lowered
by 30 versus chemotherapy plus placebo Six years after the treatment 78 of patients were alive Drugs in RampD 9 (2) 131ndash5 2008
Looking to the past may help planning for thefuture
However γδ T cells are peculiar in that they do not seem to require antigen processing and major-histocompatibility-complex (MHC) presentation of peptide epitopes although some recognize MHC class Ib molecules Furthermore γδ T cells are believed to have a prominent role in recognition of lipid antigens
Imiquimod
Imiquimod (INN) is a prescription medication that acts as an immune response modifier and is used to treat genital warts superficial basal cell carcinoma and actinic keratosis Imiquimod signals to the innate arm of the immune system through the toll-like receptor 7 (TLR7)
Plasmacytoid dendritic cells (pDCs) are innate immune cells that circulate in the blood and are found in peripheral lymphoid organs They constitute lt 04 of peripheral blood mononuclear cells (PBMC) In humans these cells express the surface markers CD123 BDCA-2(CD303) and BDCA-4 (CD304) but do not express high levels of CD11c or CD14 which distinguishes them from conventional dendritic cells or monocytes respectively
TNF-related apoptosis-inducing ligand (TRAIL) is aprotein functioning as a ligand that induces the process of cell death called apoptosis TRAIL is a cytokine that is produced and secreted by most normal tissue cells It causes apoptosis primarily in tumor cells by binding to certain death receptors TRAIL has also been designated CD253 (cluster of differentiation 253)
Melanoma in situ ndash Lentigo malignaImiquimod Treatment
Mifamurtide (Mepactreg Takeda) is a drug against osteosarcoma
mainly affecting children and young adults which is lethal in about a third of cases The drug was approved in Europe in March 2009
In a phase-III clinical trial in about 800 newly diagnosed osteosarcoma patients
mifamurtide was combined with the chemotherapeutic agents doxorubicin and
methotrexate with or without cisplatin and ifosfamide The mortality could be lowered
by 30 versus chemotherapy plus placebo Six years after the treatment 78 of patients were alive Drugs in RampD 9 (2) 131ndash5 2008
Looking to the past may help planning for thefuture
Imiquimod
Imiquimod (INN) is a prescription medication that acts as an immune response modifier and is used to treat genital warts superficial basal cell carcinoma and actinic keratosis Imiquimod signals to the innate arm of the immune system through the toll-like receptor 7 (TLR7)
Plasmacytoid dendritic cells (pDCs) are innate immune cells that circulate in the blood and are found in peripheral lymphoid organs They constitute lt 04 of peripheral blood mononuclear cells (PBMC) In humans these cells express the surface markers CD123 BDCA-2(CD303) and BDCA-4 (CD304) but do not express high levels of CD11c or CD14 which distinguishes them from conventional dendritic cells or monocytes respectively
TNF-related apoptosis-inducing ligand (TRAIL) is aprotein functioning as a ligand that induces the process of cell death called apoptosis TRAIL is a cytokine that is produced and secreted by most normal tissue cells It causes apoptosis primarily in tumor cells by binding to certain death receptors TRAIL has also been designated CD253 (cluster of differentiation 253)
Melanoma in situ ndash Lentigo malignaImiquimod Treatment
Mifamurtide (Mepactreg Takeda) is a drug against osteosarcoma
mainly affecting children and young adults which is lethal in about a third of cases The drug was approved in Europe in March 2009
In a phase-III clinical trial in about 800 newly diagnosed osteosarcoma patients
mifamurtide was combined with the chemotherapeutic agents doxorubicin and
methotrexate with or without cisplatin and ifosfamide The mortality could be lowered
by 30 versus chemotherapy plus placebo Six years after the treatment 78 of patients were alive Drugs in RampD 9 (2) 131ndash5 2008
Looking to the past may help planning for thefuture
Plasmacytoid dendritic cells (pDCs) are innate immune cells that circulate in the blood and are found in peripheral lymphoid organs They constitute lt 04 of peripheral blood mononuclear cells (PBMC) In humans these cells express the surface markers CD123 BDCA-2(CD303) and BDCA-4 (CD304) but do not express high levels of CD11c or CD14 which distinguishes them from conventional dendritic cells or monocytes respectively
TNF-related apoptosis-inducing ligand (TRAIL) is aprotein functioning as a ligand that induces the process of cell death called apoptosis TRAIL is a cytokine that is produced and secreted by most normal tissue cells It causes apoptosis primarily in tumor cells by binding to certain death receptors TRAIL has also been designated CD253 (cluster of differentiation 253)
Melanoma in situ ndash Lentigo malignaImiquimod Treatment
Mifamurtide (Mepactreg Takeda) is a drug against osteosarcoma
mainly affecting children and young adults which is lethal in about a third of cases The drug was approved in Europe in March 2009
In a phase-III clinical trial in about 800 newly diagnosed osteosarcoma patients
mifamurtide was combined with the chemotherapeutic agents doxorubicin and
methotrexate with or without cisplatin and ifosfamide The mortality could be lowered
by 30 versus chemotherapy plus placebo Six years after the treatment 78 of patients were alive Drugs in RampD 9 (2) 131ndash5 2008
Looking to the past may help planning for thefuture
TNF-related apoptosis-inducing ligand (TRAIL) is aprotein functioning as a ligand that induces the process of cell death called apoptosis TRAIL is a cytokine that is produced and secreted by most normal tissue cells It causes apoptosis primarily in tumor cells by binding to certain death receptors TRAIL has also been designated CD253 (cluster of differentiation 253)
Melanoma in situ ndash Lentigo malignaImiquimod Treatment
Mifamurtide (Mepactreg Takeda) is a drug against osteosarcoma
mainly affecting children and young adults which is lethal in about a third of cases The drug was approved in Europe in March 2009
In a phase-III clinical trial in about 800 newly diagnosed osteosarcoma patients
mifamurtide was combined with the chemotherapeutic agents doxorubicin and
methotrexate with or without cisplatin and ifosfamide The mortality could be lowered
by 30 versus chemotherapy plus placebo Six years after the treatment 78 of patients were alive Drugs in RampD 9 (2) 131ndash5 2008
Looking to the past may help planning for thefuture
Melanoma in situ ndash Lentigo malignaImiquimod Treatment
Mifamurtide (Mepactreg Takeda) is a drug against osteosarcoma
mainly affecting children and young adults which is lethal in about a third of cases The drug was approved in Europe in March 2009
In a phase-III clinical trial in about 800 newly diagnosed osteosarcoma patients
mifamurtide was combined with the chemotherapeutic agents doxorubicin and
methotrexate with or without cisplatin and ifosfamide The mortality could be lowered
by 30 versus chemotherapy plus placebo Six years after the treatment 78 of patients were alive Drugs in RampD 9 (2) 131ndash5 2008
Looking to the past may help planning for thefuture
Mifamurtide (Mepactreg Takeda) is a drug against osteosarcoma
mainly affecting children and young adults which is lethal in about a third of cases The drug was approved in Europe in March 2009
In a phase-III clinical trial in about 800 newly diagnosed osteosarcoma patients
mifamurtide was combined with the chemotherapeutic agents doxorubicin and
methotrexate with or without cisplatin and ifosfamide The mortality could be lowered
by 30 versus chemotherapy plus placebo Six years after the treatment 78 of patients were alive Drugs in RampD 9 (2) 131ndash5 2008
Looking to the past may help planning for thefuture
Looking to the past may help planning for thefuture