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US 11,026,973 B2Granted
Engineered phagocytic receptor compositions and methods of use thereof
AssigneeMyeloid Therapeutics, Inc.
InventorsDaniel Getts, Yuxiao Wang
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Abstract
The present disclosure provides compositions and methods for making and using engineered killer phagocytic cells for immunotherapy in cancer or infection by expressing a chimeric antigen receptor having an enhanced phagocytic activity, the chimeric receptor is encoded by a recombinant nucleic acid.
Claims16
A pharmaceutical composition comprising:
- (a) myeloid cells from a human subject comprising a recombinant polynucleic acid, wherein the myeloid cells are CD14+ and CD16−, and wherein the recombinant polynucleic acid comprises a sequence encoding a chimeric fusion protein (CFP), the CFP comprising:
- (i) an extracellular domain comprising a CD5 binding domain, wherein the CD5 binding domain comprises an scFv comprising a variable heavy chain (VH) sequence with SEQ ID NO:
- 1 and a variable light chain (VL) sequence with SEQ ID NO:
- 2,
- (ii) a CD8 transmembrane domain operatively linked to the extracellular domain;
- and
- (iii) an intracellular domain comprising at least two intracellular signaling domains, wherein the at least two intracellular signaling domains comprise:
- (A) a first intracellular signaling domain derived from FcγR or FcεR, and
- (B) a second intracellular signaling domain comprising a PI3K recruitment domain;
- and
- (b) a pharmaceutically acceptable carrier;
- wherein the myeloid cells express the CFP and exhibit at least a 1.1 fold increase in phagocytosis of a target cell expressing CD5;
- and
- wherein the pharmaceutical composition comprises an effective amount of the myeloid cells to inhibit growth of a solid tumor when administered to a human subject with the solid tumor.
11 more elements
Dependencies are inferred from the claim text.