natural killer (nk) cells for cancer therapies dr. dirk ... · pdf filefit for health and...
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FP7 Health Partnering event
30 May 2012, Brussels
Fit for Health and HEALTH-NCP-NET projects are funded by the European Commission
Natural Killer (NK) cells for cancer therapies
Dr. Dirk Groenewegen
Glycostem Therapeutics
Diseases and Ageing
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NK cells arise from hematopoietic
stem and progenitor cells
NKTB (CLP) B cells
T cells
NK cells
DCs
Monocytes/Macrophages
Granulocytes
Megakaryocytes/Platelets
Erythrocytes
MNKTB
MNK
MENKTB (HSC)
MENK
ME (CMP)
M
E
CD34+
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Nokilling
Normal cell
MHC class Imolecule
- +Inhibitoryreceptor
Activatingreceptor
Activatingligand
Transformation
Yeskilling
Tumor cell
+
Missing-self recognition
of tumor cells
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Fit for Health and HEALTH-NCP-NET projects are funded by the European Commission
• NK-cells are capable of eliminating cancer cells
• Clinical results acute myeloid leukemia reported
• Bottlenecks for therapeutic breakthrough
• number of NK-cells
• activation status
• contamination with B- and T-cells
• Ex-vivo generated NK-cells overcome bottlenecks
NK-cells for cancer therapies
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Requirements
� high NK cell purity
� high NK cell yield
� high NK cell functionality
� clinical grade manufacturing
� devoid of T- and B-cells
GMP ex-vivo generation
allogeneic NK cell products:
+
Spanholtz et al., PlosOne 2011
CliniMACS CD34 selection
Washing &volume reduction
NK cell generationThawing of
cryopreserved UCB Product release
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NK cell-mediated killing of melanoma cells
Movie shows 1st hour of co-culture
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Acute MyeloidLeukemia
Five-year survival is ~40% for younger and only 10% for older patients!
ChemotherapyStem cell transplant
Targeted drugs
AML patient in CRor with smoldering/residual disease
after chemotherapy and SCT
Flu 30 mg/m2Cy 900 mg/m2on day -6 to -3
Trial objectives
�Feasibility, Safety and Toxicity�In vivo survival time and expansion of transfused NK cells�Biological activity of transfused NK cells�Effect on residual disease determined by AML-MRD PCR
Allo-NK cell infusion
UCB unit Ex vivo exp & diff protocol
Phase I dose escalationstudy in AML patients
Escalating dosages:3x10^6/kg (n=3)
10x10^6/kg (n=3)30x10^6/kg (n=3)
100x10^6/kg (n=3)
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8
Objective : Build a cell therapy platform
phase I
AML
phase I
Disease B
cell AML
experimentscell B
experiments
cell C
experiments
Cell DE
experiments
Xenograft
Studies B
Xenograft
Studies C
phase I
Disease C
Xenograft
Studies D
Xenograft
Studies AML
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Topic
Fit for Health and HEALTH-NCP-NET projects are funded by the European Commission
Evaluate NK-cell interventions in
preclinical and clinical settings for :
• Leukemia's & Leukemic Disorders
• Solid Tumors : Skin, Breast, Colon, Liver, Lung
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Fit for Health and HEALTH-NCP-NET projects are funded by the European Commission
Summary of Propositon
Glycostem Therapeutics’ expertise:
• GMP-compliant NK-cellular products
Partners sought:
• Academic leaders in preclinical and clinical evaluation of
immunotherapy
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Thank you!
Contact details
Fit for Health and HEALTH-NCP-NET projects are funded by the European Commission
Dr. Dirk Groenewegen
Glycostem Therapeutics (SME)
Netherlands