CPC A61K 35/17 (2013.01) [A61K 9/0019 (2013.01); A61K 9/0085 (2013.01); A61K 31/664 (2013.01); A61K 31/7076 (2013.01); A61K 35/28 (2013.01); A61K 38/177 (2013.01); A61K 38/1774 (2013.01); A61K 38/193 (2013.01); A61K 38/4873 (2013.01); A61K 38/52 (2013.01); A61K 39/39 (2013.01); A61K 39/3955 (2013.01); A61K 45/06 (2013.01); C12N 5/0636 (2013.01); C12N 9/1241 (2013.01); C12N 9/22 (2013.01); C12N 15/11 (2013.01); C12Y 207/07 (2013.01); C12Y 304/22062 (2013.01); C12Y 502/01008 (2013.01); C12N 2310/20 (2017.05); C12N 2510/00 (2013.01); C12N 2800/80 (2013.01)] | 19 Claims |
1. A method of eliminating at least one target hematopoietic stem cell (HSC) in a subject, comprising administering to the subject an effective amount of a composition comprising a plurality of T-cells that express at least one chimeric ligand receptor (CLR) that specifically binds to c-KIT,
wherein the specific binding of the at least one CLR to c-KIT activates the T-cell,
wherein the activated T-cell induces death of the at least one target HSC, and
wherein the at least one CLR comprises:
(a) an ectodomain comprising
i) a signal peptide comprising a human CD8α signal peptide;
ii) a scFv comprising the amino acid sequence of SEQ ID NO: 73; and
iii) a hinge domain comprising a human CD8α hinge domain;
(b) a transmembrane domain comprising a human CD8α transmembrane domain;
(c) a co-stimulatory domain comprising a human 4-1BB costimulatory domain; and
(d) a endodomain comprising a human CD3ζ endodomain.
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