Chemically controlled monoclonal antibody target engagement
AssigneeThe Regents of the University of California
InventorsCharles S. CRAIK, Kevan M. SHOKAT, Ziyang ZHANG, Peter J. ROHWEDER
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Abstract
The present disclosure relates generally to antibodies reactive with tumor-specific neoantigens, as well as neoantigen-binding fragments thereof. The present disclosure also relates to nucleic acids, expression cassettes, and expression vectors encoding the antibodies and neoantigen-binding fragments. The antibodies and neoantigen binding-fragments are useful for diagnosis and treatment of cancer.
Claims23
An antibody or antigen binding fragment thereof, wherein the antibody or fragment binds to an antigen comprising the amino acid sequence GAC(1620)GVGKSAL (SEQ ID NO:2) but not the amino acid sequence GACGVGKSAL (SEQ ID NO:1).
2-19. (canceled)
21-25. (canceled)
A method for treating cancer, the method comprising:
- administering to a patient with cancer an effective amount of a targeted covalent inhibitor of an oncoprotein expressed in cells of the cancer such that a neoantigen is formed by binding of the inhibitor to the oncoprotein;
- and
- administering to the patient an effective amount of a neoantigen-specific antibody or antigen-binding fragment thereof.
A method for identifying a neoantigen-specific antibody, the method comprising:
- (a) providing a neoantigen comprising a targeted covalent inhibitor bound to an acquired cysteine residue of an oncoprotein fragment, wherein the fragment is from 8-18 residues in length;
- (b) contacting the neoantigen with a library comprising a plurality of antibodies under conditions suitable for binding at least one antibody of the plurality of antibodies to the neoantigen;
- and
- (c) recovering the at least one antibody bound to the neoantigen.
(canceled)
Dependencies are inferred from the claim text.