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. A pharmaceutical composition, comprising:
(a) a monoclonal antibody or antigen-binding fragment thereof, comprising:
i) a light chain CDR1 having the amino acid sequence set forth as SEQ ID NO: 1, a light chain CDR2 having the amino acid sequence set forth as SEQ ID NO: 2, a light chain CDR3 having the amino acid sequence set forth as SEQ ID NO: 3; and
ii) a heavy chain CDR1 having the amino acid sequence set forth as SEQ ID NO: 4, a heavy chain CDR2 having the amino acid sequence set forth as SEQ ID NO: 5, and a heavy chain CDR3 having the amino acid sequence set forth as SEQ ID NO: 6;
wherein the monoclonal antibody or antigen-binding fragment thereof binds to at least two complexes comprising (i) HLA-E and (ii) a peptide having 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); and
(b) a pharmaceutically acceptable carrier or excipient.
2. The pharmaceutical composition of claim 1 , wherein the monoclonal antibody or antigen-binding fragment thereof comprises: a VL comprising an amino acid sequence with 90% identity to the amino acid sequence set forth as SEQ ID NO: 7; and a VH comprising an amino acid sequence with 90% identity to the amino acid sequence set forth as SEQ ID NO: 8.
3. The pharmaceutical composition of claim 1 , wherein the monoclonal antibody or antigen-binding fragment thereof comprises: a VL comprising the amino acid sequence set forth as SEQ ID NO: 7; and a VH comprising the amino acid sequence set forth as SEQ ID NO: 8.
4. The pharmaceutical composition of claim 1 , wherein the monoclonal antibody or antigen-binding fragment thereof does not have a binding affinity to (i) the HLA-E alone; or (ii) the peptide alone.
5. A bispecific T cell engager antibody, comprising the monoclonal antibody of claim 1 , or an antigen binding fragment thereof.
6. The bispecific T cell engager antibody or antigen-binding fragment thereof of claim 5 , wherein the bispecific T cell engager antibody or antigen-binding fragment thereof further comprises:
a means of binding to CD3 on a T cell receptor.
7. The bispecific T cell engager antibody or antigen-binding fragment thereof of claim 6 , wherein the means of binding to CD3 on the T cell receptor comprises an anti-CD3 antibody or antigen-binding fragment thereof.
8. The bispecific T cell engager antibody or antigen-binding fragment thereof of claim 5 , wherein the bispecific T cell engager antibody or antigen-binding fragment thereof does not have a binding affinity to (i) the HLA-E alone; or (ii) the peptide alone.