Compositions and methods for immunotherapy of NPM1c-positive cancer
AssigneeMassachusetts Institute of Technology
InventorsJianzhu Chen, Guozhu Xie
Life of this patent
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Abstract
The present disclosure relates to compounds (e.g., antibodies, antigen-binding fragments thereof, bispecific molecules, or chimeric antigen receptor polypeptides) that bind to a neoepitope of mutant nucleophosmin (NPM1c) in complex with, or presented by, a class I major histocompatibility complex (MHC class I) protein, or cells expressing such compounds, and their use in methods for treating, or ameliorating one or more symptoms of, cancer.
Claims82
An antibody, or antigen binding fragment thereof, that specifically binds to an antigen comprising an NPM1c neoepitope in complex with a class I major histocompatibility complex (MHC class I) protein, wherein the antibody, or antigen binding fragment comprises:
- (a) a heavy chain variable region (VH), wherein the VH comprises VH complementarity determining region (CDR)1, VH CDR2 and VH CDR3, wherein the VH CDR1 has the amino acid sequence GFTFSSYA (SEQ ID NO:9), the VH CDR2 has the amino acid sequence ISGSGGST (SEQ ID NO:10), and the VH CDR3 has the amino acid sequence ARLGYPTTTLLPFDY (SEQ ID NO:11);
- and
- (b) a light chain variable region (VL), wherein the VL comprises VL complementarity determining region (CDR)1, VL CDR2 and VL CDR3, wherein the VL CDR1 has the amino acid sequence QSISSY (SEQ ID NO:6), the VL CDR2 has the amino acid sequence AAS (SEQ ID NO:7), and the VL CDR3 has the amino acid sequence QQSYSTPLT (SEQ ID NO:8).
A pharmaceutical composition comprising a therapeutically effective amount of an antibody, or antigen binding fragment thereof, that specifically binds to a n antigen comprising an NPM1c neoepitope in complex with a class I major histocompatibility complex (MHC class I) protein, and a pharmaceutically acceptable carrier, wherein the antibody, or antigen binding fragment comprises:
- (a) a heavy chain variable region (VH), wherein the VH comprises VH complementarity determining region (CDR)1, VH CDR2 and VH CDR3, wherein the VH CDR1 has the amino acid sequence GFTFSSYA (SEQ ID NO:9), the VH CDR2 has the amino acid sequence ISGSGGST (SEQ ID NO:10), and the VH CDR3 has the amino acid sequence ARLGYPTTTLLPFDY (SEQ ID NO:11);
- and
- (b) a light chain variable region (VL), wherein the VL comprises VL complementarity determining region (CDR)1, VL CDR2 and VL CDR3, wherein the VL CDR1 has the amino acid sequence QSISSY (SEQ ID NO:6), the VL CDR2 has the amino acid sequence AAS (SEQ ID NO:7), and the VL CDR3 has the amino acid sequence QQSYSTPLT (SEQ ID NO:8).
Dependencies are inferred from the claim text.