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 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 .