Anti-CXCR2 antibodies and uses thereof
Provided are anti-CXCR2 antibodies and antigen-binding fragments thereof. The antibodies or fragments thereof specifically bind to N-terminal, extracellular domain of the CXCR2 protein. In various example, the antibodies or fragments thereof include a VH CDR1 of SEQ ID NO: 1, a VH CDR2 of SEQ ID NO: 2, a VH CDR3 of SEQ ID NO: 3, or any one of SQ ID NO: 7-14, a VL CDR1 of SEQ ID NO: 4, a VL CDR2 of SEQ ID NO: 5, and a VL CDR3 of SEQ ID NO: 6, or variants of each thereof. Methods of using the antibodies or fragments thereof for treating and diagnosing diseases such as cancer and inflammatory diseases are also provided.
1 . An antibody or fragment thereof, wherein the antibody or fragment thereof has specificity to a human C—X—C Motif Chemokine Receptor 2 (CXCR2) protein and comprises a heavy chain variable region (VH) comprising a CDR1, a CDR2 and a CDR3, and a light chain variable region (VL) comprising a CDR1, a CDR2 and a CDR3, wherein:
the V H CDR1 comprises the amino acid sequence of SEQ ID NO:1;
the V H CDR2 comprises the amino acid sequence of SEQ ID NO:2;
the V H CDR3 comprises the amino acid sequence of SEQ ID NO:3, or a variant selected from the group consisting of SEQ ID NO:7-14;
the VL CDR1 comprises the amino acid sequence of SEQ ID NO:4;
the VL CDR2 comprises the amino acid sequence of SEQ ID NO:5; and
the VL CDR3 comprises the amino acid sequence of SEQ ID NO:6.
2 . The antibody or fragment thereof of claim 1 , wherein the VH CDR3 comprises the amino acid sequence of SEQ ID NO:3.
3 . The antibody or fragment thereof of claim 1 , further comprising a heavy chain constant region, a light chain constant region, an Fc region, or the combination thereof.
4 . The antibody or fragment thereof of claim 1 , wherein the antibody is a human antibody.
5 . The antibody or fragment thereof of claim 1 , wherein the VH comprises the amino acid sequence of SEQ ID NO:17 or 18, or a peptide having at least 90% sequence identity to SEQ ID NO:17 or 18.
6 . The antibody or fragment thereof of claim 1 , wherein the VH comprises the amino acid sequence of SEQ ID NO:18, or a peptide having at least 90% sequence identity to SEQ ID NO:18.
7 . The antibody or fragment thereof of claim 5 , wherein the VL comprises the amino acid sequence of SEQ ID NO:19, or a peptide having at least 90% sequence identity to SEQ ID NO:19.
8 . One or more polynucleotide encoding the antibody or fragment thereof of claim 1 .
9 . A method of treating an neutrophil-related inflammatory disease in a patient in need thereof, comprising administering to the patient an effective amount of the antibody or fragment thereof of claim 1 .
10 . A method of treating cancer in a patient in need thereof, comprising administering to the patient an effective amount of the antibody or fragment thereof of claim 1 , wherein the cancer is selected from the group consisting of bladder cancer, liver cancer, colon cancer, rectal cancer, leukemia, lymphoma, pancreatic cancer, small cell lung cancer, non-small cell lung cancer, breast cancer, head and neck cancer, gastrointestinal cancer, stomach cancer, esophageal cancer, ovarian cancer, renal cancer, melanoma, prostate cancer and thyroid cancer.
11 . The method of claim 9 , wherein the neutrophil-related inflammatory disease is selected from the group consisting of arthritis, rheumatoid arthritis, multiple sclerosis, psoriasis, psoriatic arthritis, Crohn's disease, inflammatory bowel disease, asthma, chronic obstructive pulmonary disease, osteoarthritis ulcerative colitis, lupus, systemic lupus erythematous, juvenile rheumatoid arthritis, juvenile idiopathic arthritis, dermatomyositis, Sjogren syndrome, type I diabetes, and atherosclerosis.
12 . The method of claim 9 , wherein the neutrophil-related inflammatory disease is caused by an infection.