gene therapy
Post on 16-Aug-2015
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GENE THERAPY FOR ORAL CANCER
WHAT IS A CANCER?
Cascade of cellular events that changes normal cell into malignant.
6th most worldwide – oral cancer.
OSCC most common , poor prognosis of max 5 year survival rate
WHAT IS GENE THERAPY?
Refers to replacing or repairing a defective gene in the diseased cell's genome in order to restore normal cell function and tissue integrity.
GENETIC BASIS OF OSCC
COMMMON GENE ALTERATIONS IN OSCC
GENE FUNCTION
TUMOUR SUPPRESSOR GENE
1. p16 senescence , cell cyle progression
2. p53 cell cyle regulation
3. PTEN signaling , migration
4. Rb gene cell cycle regulation
PROTOONCOGENES
1. CyclinD1 cell cycle regulation
2. Epidermal growth factor cell proliferation
3. p63 unknown
TYPES OF GENE THERAPY
GERMLINE GENE THERAPYGERMLINE GENE THERAPY
SOMATIC GENE THERPYSOMATIC GENE THERPY
GERM LINE THERAPY
SOMATIC THERAPY
Gene insertion Into germ cells into body cells
Modification Inherited by offspring
Restricted to individual
Safety Not ethically safe
Ethically sound & safe
STEPS IN GENE THERAPY
Identification and amplification of affected gene
Extraction and invitro culture
Transfer of therapeutic gene via vector
Transfer of corrected gene into the patient.
MODES OF TRANSMISSION
TECHNIQUES OF GENE THERAPY
GENE ADDITION THERAPY
Regulates tumour growth
Addition of tumour suppressor gene
p53
Induce apoptosis
GENE EXCISION THERAPY
Inhibits tumour growth
Removes defective oncogene
Egr-1(Early growth response factor)
Inhibits cell division
ANTI-SENSE RNA THERAPY
Gene expression inhibited by RNA.
Prevents activity of oncogenes – myc , ras and fos.
Inhibits virus – HPV1 , HTLV . HSV1.
SUCIDE GENE THERAPY
Genes are introduced – stimulates generation of products – toxic to the tumour cells.
Enables prodrug to active cytotoxic drug
IMMUNE THERAPY Increases patients immune
response to fight tumour
Increases efficacy of NK cells , T cells and cytokines
TYPES : 1.Therapeutic cancer vaccines
2.Monoclonal antibodies
3.Checkpoint inhibitors
4.Cytokines
PATHOPHYSIOLOGY OF IMMUNE THERAPY
GENE THERAPY BY ONCOLYTIC VIRUS Effective therapy
Virus are genetically modified
Which replicates & lyses tumour cells
Virus – HSV , chiefly Adeno virus
Adeno ONYX -015 lacks del of E1B region , contains p53
ADENO VIRUS : KEY VECTOR
UNIQUE viral structure
Capacity to hold large segments of DNA.
Easy manipulation
Produce high titers
Doesn’t integrate in the genomes
High transduction efficacy.
ADVEXIN Adenovirus type5 , E1 region
replaced by cDNA p53gene.
On introduction , cell growth arrests , apoptosis of tumour cells
Advexin intratumoural + Chemotherapy (Cisplastine , 5-flouracil ) + immunotherapy = positive result.
ONYX dl1520 Replicational condition virus ,
lacks E1B region , binds to & inactivates p53.
Tumour cells(p53 deficient) , allows rapid viral replication and kills tumour cells.
ONYX mouthwashes efficient – epithelial dysplasia and leukoplakia.
DEMERITS OF GENE THERAPY
Increased potentiality for toxicity & inflammatory response
Effectiveness of therapy can be reduced by host immune response
Intro of DNA in wrong place of genome – induce a tumour
Long term treatment
Technique sensitive
MERITS OF GENE THERAPY
Better prognosis
Targets specifically tumour cells
Cost effective
Lesser painful and discomfort
CONCLUSION
ONGOING RESEARCH IN LABORATORY AND CLINICS
PRESENT – ALTEREDADENOVIRUS+CHEMOTHERAPY+IMMUNOTHERAPY =POSITIVE RESULT
FUTURE AND BETTER SCOPE OF TREATMENT
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