Expansion and use of expanded nk cell fractions
AssigneeGamida Cell Ltd.
InventorTony PELED
Life of this patent
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Abstract
Methods of expanding a natural killer (NK) cell fraction for transplantation into a subject are provided, and particularly, methods for providing transplantable NK cell fractions and protocols for their use, which can be employed for applications in cell transplants and infusions for treatment of cancer and other disease.
Claims39
A method of preparing a transplantable NK cell fraction for transplantation into a subject in need thereof, the method comprising:
- (a) obtaining a CD3-depleted NK cell fraction HLA-haploidentical or HLA-mismatched for said subject;
- (b) ex vivo culturing said CD3-depleted NK cell fraction under conditions allowing for cell proliferation, wherein said conditions comprise providing nutrients, serum, IL-15 and nicotinamide in an amount between 1.0 mM to 10 mM;
- (c) supplementing said CD3-depleted NK cell fraction with fresh nutrients, serum, IL-15 and nicotinamide 8-10 days following step (b) to produce an expanded CD3-depleted NK cell fraction;
- (d) harvesting said expanded CD3-depleted NK cell fraction 14-16 days following step (b);
- and
- (e) washing and concentrating said expanded CD3-depleted NK cell fraction of step (d),
- thereby producing a transplantable NK cell fraction for transplantation in said subject.
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A transplantable human NK cell fraction characterized by the following parameters:
- (a) at least 70% CD56+/CD3− cells;
- (b) at least 70% viability;
- (c) fewer than 5.0×105 CD3+ cells/Kg mass of patient, upon infusion;
- (d) no more than 5 EU endotoxin/Kg mass of patient, upon infusion;
- and
- (e) no Gram-positive micro-organisms.
A method of treating a hematological disease in a human subject in need thereof, the method comprising:
- (a) administering an anti-cancer monoclonal antibody to said subject;
- (b) administering at least one immunosuppressive agent to said subject;
- (c) transplanting an expanded CD3-depleted haploidentical or mismatched NK cell fraction into said subject in need thereof, wherein said expanded CD3-depleted HLA-haploidentical or HLA-mismatched NK cell fraction has been expanded by ex-vivo culturing with nutrients, serum, IL-15 and nicotinamide in an amount between 1.0 mM to 10 mM;
- and
- (d) administering IL-2 to said subject,
- thereby treating said hematological disease in said subject.
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Dependencies are inferred from the claim text.