Antibodies targeting a complex comprising non-classical hla-i and neoantigen and their methods of use

Abstract

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.