SIRPalpha Knockout iPSC-derived and CAR-comprising Macrophages with Enhanced Anti-tumor Activity
AssigneeWisconsin Alumni Research Foundation
InventorsPortia Smith, Jue Zhang, Igor I. Slukvin
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Abstract
Provided herein are methods for reducing or eliminating tumor cell growth using genetically engineered macrophages having modified embodiments of signal regulatory protein alpha (SIRPα) gene resulting in reduced or ablated expression thereof, wherein the tumor cell reducing or eliminating activity of the macrophages is not subject to macrophage exhaustion. Therapeutically effective populations of such genetically engineered macrophages are also provided.
Claims28
1-2. (canceled)
A method of treating a subject bearing a SIRPα ligand-expressing tumor, or reducing the growth of signal regulatory protein alpha (SIRPα) ligand-expressing tumor cells, comprising contacting the tumor with an effective amount of a combination of SIRPA knockout macrophages, wherein the SIRPA knockout macrophages:
- (a) are administered in combination with an antibody immunologically specific for the tumor cells;
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- (b) express a chimeric antigen receptor (CAR) that is immunologically specific for the tumor cells:
- wherein the tumor cell reducing or eliminating activity of the SIRPA-KO macrophages is characterized by reduced macrophage exhaustion thereby.
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23-24. (canceled)
A homogenous population of modified macrophages, wherein the modified macrophages are SIRPA knockout macrophages with a tumor-killing capacity phenotype exhibiting heightened capacity for antibody-dependent and CAR-dependent cellular phagocytosis without experiencing hypophagia.
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Dependencies are inferred from the claim text.