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 antigen-binding fragment thereof comprising a heavy chain (HC) comprising an amino acid sequence set forth as SEQ ID NO: 30. 
     
     
         240 . The monoclonal antibody of  claim 239  or antigen-binding fragment thereof comprising a light chain (LC) comprising an amino acid sequence set forth as SEQ ID NO: 31. 
     
     
         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: 32. 
     
     
         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: 31. 
     
     
         246 - 248 . (canceled) 
     
     
         249 . A monoclonal antibody or antigen-binding fragment thereof comprising a HC comprising an amino acid sequence set forth as SEQ ID NO: 33. 
     
     
         250 . The monoclonal antibody of  claim 249  or an antigen-binding fragment thereof, comprising a LC comprising an amino acid sequence set forth as SEQ ID NO: 31. 
     
     
         251 .- 259 . (canceled) 
     
     
         260 . The monoclonal antibody of any one of  claims 239 ,  244 , or  249 , wherein the monoclonal antibody or antigen-binding fragment thereof selectively binds to at least two complexes comprising an HLA-E and a neoantigen comprising a sequence selected from the group consisting of SEQ ID NO: 17 (VMAPRTLIL), SEQ ID NO: 18 (VMAPRTLFL), SEQ ID NO: 19 (VMAPRTLVL), SEQ ID NO: 20 (VTAPRTLLL), SEQ ID NO: 21 (IMAPRTLVL), SEQ ID NO: 23 (VMAPQALLL), SEQ ID NO: 24 (VMAPRALLL), SEQ ID NO: 25 (VMAPRTLLL), SEQ ID NO: 26 (VMAPRTLTL), SEQ ID NO: 27 (VMAPRTVLL), SEQ ID NO: 28 (VMPPRTLLL), or SEQ ID NO: 29 (VTAPRTVLL). 
     
     
         261 .- 282 . (canceled) 
     
     
         283 . A bispecific T cell engager, comprising:
 (a) a HC comprising an amino acid sequence set forth as SEQ ID NO: 30; and   (b) a means for binding to a CD3 protein associated with a T cell receptor (TCR).   
     
     
         284 . The bispecific T cell engager of  claim 283 , further comprising a LC comprising an amino acid sequence set forth as SEQ ID NO: 31. 
     
     
         285 . A pharmaceutical composition comprising:
 (a) a monoclonal antibody or an antigen-binding fragment thereof according to  claim 239 ,  244 , or  249 , or the bispecific T cell engager according to  claim 283 ; and   (b) a pharmaceutically acceptable carrier or excipient.   
     
     
         286 . A method of treating an HLA-E-expressing cancer in an individual in need thereof, comprising administering to the individual an effective amount the pharmaceutical composition of  claim 285 .