Mesothelin-targeted chimeric antigen receptors and methods of making them
AssigneesMemorial Sloan Kettering Cancer Center, The U.S.A., as represented by the Secretary, Department of Health and Human Services
InventorsPrasad S. Adusumilli, Michel Sadelain, Dimiter S. Dimitrov, Yang Feng
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Abstract
The presently disclosed subject matter provides for methods and compositions for enhancing the immune response toward cancers and pathogens. It relates to chimeric antigen receptors (CARs) that specifically target human mesothelin, and immunoresponsive cells comprising such CARs. The presently disclosed mesothelin-targeted CARs have enhanced immune-activating properties, including anti-tumor activity.
Claims29
A chimeric antigen receptor (CAR), comprising an extracellular antigen-binding domain, a transmembrane domain and an intracellular domain, wherein the extracellular antigen-binding domain comprises a single-chain variable fragment (scFv), wherein the scFv comprises:
- (a) a heavy chain variable region CDR1 comprising the amino acid sequence set forth in SEQ ID NO:11, (b) a heavy chain variable region CDR2 comprising the amino acid sequence set forth in SEQ ID NO:12, (c) a heavy chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:13, (d) a light chain variable region CDR1 comprising the amino acid sequence set forth in SEQ ID NO:14, (e) a light chain variable region CDR2 comprising the amino acid sequence set forth in SEQ ID NO:15, and (f) a light chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:16.
A method for producing an immunoresponsive cell that binds to human mesothelin, comprising introducing into the immunoresponsive cell a nucleic acid sequence that encodes a chimeric antigen receptor (CAR) comprising an extracellular antigen-binding domain, a transmembrane domain and an intracellular domain, wherein the extracellular antigen-binding domain comprises a single-chain variable fragment (scFv), wherein the scFv comprises:
- (a) a heavy chain variable region CDR1 comprising the amino acid sequence set forth in SEQ ID NO:11, (b) a heavy chain variable region CDR2 comprising the amino acid sequence set forth in SEQ ID NO:12, (c) a heavy chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:13, (d) a light chain variable region CDR1 comprising the amino acid sequence set forth in SEQ ID NO:14, (e) a light chain variable region CDR2 comprising the amino acid sequence set forth in SEQ ID NO:15, and (f) a light chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:16.
Dependencies are inferred from the claim text.