T cell receptors targeting PIK3CA mutations and uses thereof
AssigneeMemorial Sloan Kettering Cancer Center
InventorsChristopher A. Klebanoff, Smita S. Chandran
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Abstract
The presently disclosed subject matter provides for methods and compositions for treating cancer (e.g., breast cancer). It relates to mutant PIK3CA-targeted TCRs that specifically target a mutant PIK3CA peptide (e.g., a human mutant PIK3CA peptide), and immunoresponsive cells comprising such TCRs. The presently disclosed mutant PIK3CA peptide-specific TCRs have enhanced immune-activating properties, including anti-tumor activity.
Claims32
A recombinant T cell receptor (TCR) comprising an extracellular domain that specifically targets a PIK3CA peptide comprising a mutation of H1047L, wherein the extracellular domain comprises:
- a) an α chain variable region CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
- 1;
- an α chain variable region CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
- 2;
- an α chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:3;
- a β chain variable region CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
- 4;
- a β chain variable region CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
- 5;
- and a β chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
- 6;
- b) an α chain variable region CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
- 25;
- an α chain variable region CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
- 26;
- an α chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
- 27;
- a β chain variable region CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
- 28;
- a β chain variable region CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
- 29;
- and a β chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
- 30;
- or c) an α chain variable region CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
- 35;
- an α chain variable region CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
- 36;
- an α chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
- 37;
- a β chain variable region CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
- 38;
- a β chain variable region CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
- 39;
- and a β chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
- 40.
Dependencies are inferred from the claim text.