Antibodies targeting a complex comprising non-classical HLA-I and neoantigen and their methods of use
View Patent ↗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 monoclonal antibody or an antigen-binding fragment thereof, comprising:
a) 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
b) 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 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).
2. The monoclonal antibody 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.
3. A bispecific T cell engager antibody, comprising the monoclonal antibody of claim 1 or an antigen-binding fragment thereof.
4. A monoclonal antibody or an antigen-binding fragment thereof, comprising:
a) a light chain variable domain (VL) comprising the amino acid sequence set forth as SEQ ID NO: 7; and
b) a heavy chain variable domain (VH) comprising the amino acid sequence set forth as SEQ ID NO: 8
wherein the monoclonal antibody 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).
5. The monoclonal antibody of claim 4 , 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.
6. A bispecific T cell engager antibody, comprising the monoclonal antibody of claim 4 , or an antigen-binding fragment thereof.
7. A method of treating an HLA-E expressing cancer in an individual in need thereof, comprising administering to the individual an effective amount of a monoclonal antibody of claim 1 or an antigen-binding fragment thereof.
8. The method of claim 7 , wherein the cancer is 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, leukemia, lymphoma, myeloma, multiple myeloma (MM), acute myeloid leukemia (AML), myelodysplastic syndrome, a B-cell malignancy, mantel cell lymphoma.
9. A method of treating an HLA-E expressing cancer in an individual in need thereof, comprising administering to the individual an effective amount of a monoclonal antibody of claim 4 or an antigen-binding fragment thereof.
10. The method of claim 9 , wherein the cancer is 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, leukemia, lymphoma, myeloma, multiple myeloma (MM), acute myeloid leukemia (AML), myelodysplastic syndrome, a B-cell malignancy, mantel cell lymphoma.
11. The bispecific T cell engager of claim 3 , wherein the bispecific T cell engager antibody binds to CD3 on a T cell receptor.
12. The bispecific T cell engager of claim 6 , wherein the bispecific T cell engager antibody binds to CD3 on a T cell receptor.