Compositions and methods for selective elimination and replacement of hematopoietic stem cells
AssigneePoseida Therapeutics, Inc.
InventorsEric M. OSTERTAG, Devon SHEDLOCK, Julian David DOWN
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Abstract
Disclosed are methods of eliminating at least one target cell in a subject, comprising administering to the subject an effective amount of a composition comprising a plurality of immune cells, wherein each immune cell of the plurality expresses one or more chimeric ligand receptor(s) (CLR(s)) that each specifically bind to a target ligand on the at least one target cell, wherein specifically binding of the one or more CLR(s) to the target activates the immune cell, and wherein the activated immune cell induces death of the target cell. Exemplary target cells include, but are not limited to, hematopoietic stem cells (HSCs).
Claims17
1-209. (canceled)
A method of treating acute myeloid leukemia (AML) in a subject, comprising administering to the subject an effective amount of a composition comprising a plurality of T cells that express a chimeric ligand receptor (CLR) that specifically binds to c-KIT, wherein the CLR comprises:
- (a) an ectodomain comprising:
- i) a signal peptide comprising a human CD8a signal peptide;
- ii) a scFv comprising the amino acid sequence of SEQ ID NO:
- 73;
- and
- iii) a hinge domain comprising a human CD8a hinge domain;
- (b) a transmembrane domain comprising a human CD8a transmembrane domain;
- (c) a co-stimulatory domain comprising a human 4-1BB costimulatory domain;
- and
- (d) an endodomain comprising a human CD3ζ endodomain.
Dependencies are inferred from the claim text.