Monoclonal antibodies and antigen binding fragments thereof for suppressing CD73 immune checkpoint and uses thereof
Provided are monoclonal antibodies and antigen binding fragments thereof for suppressing a CD73 immune checkpoint, and uses thereof, wherein the antibodies or antigen binding fragments thereof can bind to CD73, reduce enzymatic activity of CD73 protein, and inhibit cancer metastasis or cancer growth, thus enabling uses thereof as therapeutic agents for cancer.
1 . A monoclonal antibody or an antigen binding fragment thereof comprising:
a heavy chain variable region comprising a heavy chain complementarity determining domain 1 (CDRH1) comprising the amino acid sequence of SEQ ID NO: 78, CDRH2 comprising the amino acid sequence of SEQ ID NO:79, and CDRH3 comprising the amino acid sequence of SEQ ID NO:80; and
a light chain variable region comprising CDRL1 comprising the amino acid sequence of SEQ ID NO:93, CDRL2 comprising the amino acid sequence of SEQ ID NO:94, and CDRL3 comprising the amino acid sequence of SEQ ID NO:95.
2 . The antibody or the antigen binding fragment thereof of claim 1 , wherein the antibody is a human antibody or chimeric antibody.
3 . A nucleic acid encoding the antibody or the antigen binding fragment thereof of claim 1 .
4 . An expression vector comprising the nucleic acid of claim 3 .
5 . A cell transformed with the expression vector of claim 4 .
6 . A composition comprising the antibody or the antigen binding fragment thereof of claim 1 .
7 . The composition of claim 6 , further comprising an immune checkpoint blockade or a chemotherapeutic agent.
8 . A method of treating cancer in a subject in need thereof, comprising administering the antibody or antigen binding fragment thereof of claim 1 to the subject, wherein the cancer is a CD73 overexpressing cancer.
9 . The method of claim 8 , wherein the cancer is breast cancer, triple-negative breast cancer (TBNC), pancreatic colorectal cancer, ovarian cancer, gastric cancer, bladder cancer, leukemia, prostate cancer, malignant melanoma, cancer, esophageal cancer, stomach cancer, head and neck cancer, lung cancer, or kidney cancer.
10 . The antibody or the antigen binding fragment thereof of claim 1 , comprising: a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:104; and a light chain variable region comprising the amino acid sequence of SEQ ID NO:105.