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 monoclonal antibody, or an antigen-binding fragment thereof, that selectively binds to a complex comprising an HLA-E and a peptide that comprises, consists essentially of, or consists of a sequence according to SEQ ID NO: 18 (VMAPRTLFL), 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.
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. The monoclonal antibody of claim 2 , wherein the peptide consists of a sequence according to SEQ ID NO: 18 (VMAPRTLFL).
4. A bispecific T cell engager, comprising the monoclonal antibody of claim 1 or an antigen binding-fragment thereof.
5. The bispecific T cell engager of claim 4 , wherein the bispecific T cell engager binds to a CD3 protein associated with a T cell receptor.
6. A monoclonal antibody, or an antigen-binding fragment thereof, that selectively binds to a complex comprising an HLA-E and a peptide that comprises, consists essentially of, or consists of a sequence according to SEQ ID NO: 18 (VMAPRTLFL), comprising:
(i) a light chain variable domain (VL) comprising the amino acid sequence set forth as SEQ ID NO: 7; and
(ii) a heavy chain variable domain (VH) comprising the amino acid sequence set forth as SEQ ID NO: 8.
7. The monoclonal antibody of claim 6 , 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.
8. The monoclonal antibody of claim 7 , wherein the peptide consists of a sequence according to SEQ ID NO: 18 (VMAPRTLFL).
9. A bispecific T cell engager, comprising the monoclonal antibody of claim 6 or an antigen-binding fragment thereof.
10. The bispecific T cell engager of claim 9 , wherein the bispecific T cell engager binds to a CD3 protein associated with a T cell receptor.
11. A method at treating a cancer that expresses both HLA-E and HLA-G 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, to thereby treat the cancer.
12. The method of claim 11 , 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, or mantel cell lymphoma.
13. A method of treating a cancer that expresses both HLA-E and HLA-G in an individual in need thereof, comprising administering to the individual an effective amount of a monoclonal antibody of claim 6 or an antigen-binding fragment thereof, to thereby treat the cancer.