ANTIBODIES TARGETING A COMPLEX COMPRISING NON-CLASSICAL HLA-I AND NEOANTIGEN AND THEIR METHODS OF USE
Provided herein are antibodies that selectively bind to complex comprising a non-classical HLA-I (e.g. HLA-E) and a neoantigen having variable heavy chain domains (VH), variable light chain domains (VL), and complementarity determining regions (CDRs) as disclosed herein, as well as methods and uses thereof.
1 .- 238 . (canceled)
239 . A monoclonal antibody or an antigen-binding fragment thereof, comprising a heavy chain (HC) comprising an amino acid sequence set forth as SEQ ID NO: 20.
240 . The monoclonal antibody of claim 239 or antigen-binding fragment thereof, comprising a light chain (LC) comprising an amino acid set forth as SEQ ID NO: 19.
241 .- 243 . (canceled)
244 . A monoclonal antibody or antigen-binding fragment thereof, comprising a HC comprising an amino acid sequence set forth as SEQ ID NO: 21.
245 . The monoclonal antibody of claim 244 or antigen-binding fragment thereof, comprising a LC comprising an amino acid sequence set forth as SEQ ID NO: 19.
246 .- 279 . (canceled)
280 . The monoclonal antibody of claim 239 or 244 or antigen-binding fragment thereof, wherein the monoclonal antibody or antigen-binding fragment thereof selectively binds to a complex comprising a HLA-E and a neoantigen comprising an amino acid sequence set forth as SEQ ID NO: 18 (VMAPRTLFL).
281 .- 302 . (canceled)
303 . A bispecific T cell engager, comprising:
(a) a HC comprising an amino acid sequence set forth as SEQ ID NO: 20; and
(b) a means for binding to a CD3 protein associated with a T cell receptor (TCR).
304 . The bispecific T cell engager of claim 303 , further comprising a LC comprising an amino acid sequence set forth as SEQ ID NO: 19.
305 . The bispecific T cell engager of claim 303 , wherein means for binding to a CD3 protein associated with a TCR comprises:
(a) a light chain variable region (VL) comprising a light chain complementarity determining region (CDR)1 having the amino acid sequence set forth as SEQ ID NO: 9, a light chain CDR2 having the amino acid sequence set forth as SEQ ID NO: 10, and a light chain CDR3 having the amino acid sequence set forth as SEQ ID NO: 11; and
(b) a heavy chain variable region (VH) comprising a heavy chain CDR1 having the amino acid sequence set forth as SEQ ID NO: 12, a heavy chain CDR2 having the amino acid sequence set forth as SEQ ID NO: 13, and a heavy chain CDR3 having the amino acid sequence set forth as SEQ ID NO: 14.
306 . The bispecific T cell engager of claim 303 , wherein the bispecific T cell engager selectively binds to a complex comprising an HLA-E and a neoantigen comprising a sequence set forth as SEQ ID NO: 18 (VMAPRTLFL).
307 . A pharmaceutical composition comprising:
(a) a monoclonal antibody of claim 239 or 244 or an antigen-binding fragment thereof, or the bispecific T cell engager of claim 303 ; and
(b) a pharmaceutically acceptable carrier or excipient.
308 . A method of treating a HLA-E-expressing cancer in an individual in need thereof, comprising administering to the individual an effective amount of the pharmaceutical composition of claim 307 .
309 . The method of claim 308 , wherein the HLA-E-expressing cancer is selected from the group consisting of breast cancer, kidney cancer, lung cancer, ovarian cancer, colorectal cancer, pancreatic cancer, choriocarcinoma, non-small cell lung carcinoma (NSCLC), gastric cancer, cervical cancer, head and neck cancer, myeloma, leukemia, and lymphoma.