natural killer (nk) cells for cancer therapies dr. dirk ... · pdf filefit for health and...
TRANSCRIPT
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
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+
Nokilling
Normal cell
MHC class Imolecule
- +Inhibitoryreceptor
Activatingreceptor
Activatingligand
Transformation
Yeskilling
Tumor cell
+
Missing-self recognition
of tumor cells
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
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
NK cell-mediated killing of melanoma cells
Movie shows 1st hour of co-culture
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)
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
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
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
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