Anti-human neurotensin receptor 1 antibody and use thereof
An isolated antibody, comprising: a heavy chain variable domain (V H ) that is at least 75% identical to the amino acid sequence of SEQ ID NO: 1; and a light chain variable domain (V L ) that is at least 75% identical to the amino acid sequence of SEQ ID NO: 2; wherein the antibody binds specifically to human neurotensin receptor 1 (hNTSR1).
1 . An isolated antibody comprising:
(a) a heavy chain CDR1 comprising the sequence of SEQ ID NO: 3, a heavy chain CDR2 comprising the sequence of SEQ ID NO: 5, a heavy chain CDR3 comprising the sequence of SEQ ID NO: 7 or SEQ ID NO: 8, a light chain CDR1 comprising the sequence of SEQ ID NO: 9, a light chain CDR2 comprising the sequence of SEQ ID NO: 10, and a light chain CDR3 comprising the sequence of SEQ ID NO: 11 or SEQ ID NO: 12;
(b) a heavy chain CDR1 comprising the sequence of SEQ ID NO: 4, a heavy chain CDR2 comprising the sequence of SEQ ID NO: 5, a heavy chain CDR3 comprising the sequence of SEQ ID NO: 6 or SEQ ID NO: 8, a light chain CDR1 comprising the sequence of SEQ ID NO: 9, a light chain CDR2 comprising the sequence of SEQ ID NO: 10, and a light chain CDR3 comprising the sequence of SEQ ID NO: 11 or SEQ ID NO: 12;
(c) a heavy chain CDR1 comprising the sequence of SEQ ID NO: 3, a heavy chain CDR2 comprising the sequence of SEQ ID NO: 5, a heavy chain CDR3 comprising the sequence of SEQ ID NO: 6, a light chain CDR1 comprising the sequence of SEQ ID NO: 9, a light chain CDR2 comprising the sequence of SEQ ID NO: 10, and a light chain CDR3 comprising the sequence of SEQ ID NO: 12;
(d) a V H sequence comprising the sequence of SEQ ID NO: 13 and a V L sequence comprising the sequence of SEQ ID NO: 14; or
(e) a V H sequence comprising the sequence of SEQ ID NO: 15 and a V L sequence comprising the sequence of SEQ ID NO: 16;
wherein the antibody binds specifically to human neurotensin receptor 1 (hNTSR1).
2 . The isolated antibody of claim 1 , wherein the antibody includes:
a heavy chain CDR1 comprising the sequence of SEQ ID NO: 4, a heavy chain CDR2 comprising the sequence of SEQ ID NO: 5, a heavy chain CDR3 comprising the sequence of SEQ ID NO: 8, a light chain CDR1 comprising the sequence of SEQ ID NO: 9, a light chain CDR2 comprising the sequence of SEQ ID NO: 10, and a light chain CDR3 comprising the sequence of SEQ ID NO: 12.
3 . The isolated antibody of claim 1 , wherein the antibody includes:
a heavy chain CDR1 comprising the sequence of SEQ ID NO: 4, a heavy chain CDR2 comprising the sequence of SEQ ID NO: 5, a heavy chain CDR3 comprising the sequence of SEQ ID NO: 6, a light chain CDR1 comprising the sequence of SEQ ID NO: 9, a light chain CDR2 comprising the sequence of SEQ ID NO: 10, and a light chain CDR3 comprising the sequence of SEQ ID NO: 12.
4 . The isolated antibody of claim 1 , wherein the antibody includes:
a heavy chain CDR1 comprising the sequence of SEQ ID NO: 3, a heavy chain CDR2 comprising the sequence of SEQ ID NO: 5, a heavy chain CDR3 comprising the sequence of SEQ ID NO: 7 or SEQ ID NO: 8, a light chain CDR1 comprising the sequence of SEQ ID NO: 9, a light chain CDR2 comprising the sequence of SEQ ID NO: 10, and a light chain CDR3 comprising the sequence of SEQ ID NO: 11.
5 . The isolated antibody of claim 1 , wherein the antibody includes:
a heavy chain CDR1 comprising the sequence of SEQ ID NO: 3, a heavy chain CDR2 comprising the sequence of SEQ ID NO: 5, a heavy chain CDR3 comprising the sequence of SEQ ID NO: 7 or SEQ ID NO: 8, a light chain CDR1 comprising the sequence of SEQ ID NO: 9, a light chain CDR2 comprising the sequence of SEQ ID NO: 10, and a light chain CDR3 comprising the sequence of SEQ ID NO: 12.
6 . The isolated antibody of claim 1 , wherein the antibody includes:
a heavy chain CDR1 comprising the sequence of SEQ ID NO: 3, a heavy chain CDR2 comprising the sequence of SEQ ID NO: 5, a heavy chain CDR3 comprising the sequence of SEQ ID NO: 6, a light chain CDR1 comprising the sequence of SEQ ID NO: 9, a light chain CDR2 comprising the sequence of SEQ ID NO: 10, and a light chain CDR3 comprising the sequence of SEQ ID NO: 12.
7 . The isolated antibody of claim 1 , wherein the antibody includes a V H sequence comprising the sequence of SEQ ID NO: 13; and a V L sequence comprising the sequence of SEQ ID NO: 14.
8 . The isolated antibody of claim 1 , wherein the antibody includes a V H sequence comprising the sequence of SEQ ID NO: 15; and a V L sequence comprising the sequence of SEQ ID NO: 16.
9 . The isolated antibody of claim 1 , wherein the antibody is a recombinant antibody, a monoclonal antibody, a chimeric antibody, a humanized antibody, an IgG1 antibody, or an antibody fragment comprising an antigen-binding site.
10 . A pharmaceutical composition, comprising the isolated antibody of claim 1 and a pharmaceutical carrier.
11 . An antibody conjugate, comprising:
the isolated antibody of claim 1 ; and
a non-antibody molecule.
12 . The antibody conjugate of claim 11 , wherein the non-antibody molecule is a polypeptide, a polymer, an oligosaccharide, a lipid, a glycolipid, a solid support, a small molecule drug, a biotin, a nucleic acid molecule, a carrier protein, or a detectable label.
13 . The antibody conjugate of claim 12 , wherein the conjugate is an antibody-drug conjugate.
14 . The antibody conjugate of claim 13 , wherein the non-antibody molecule is a cancer drug for treating a tumor that expresses hNTSR1.
15 . The antibody conjugate of claim 14 , wherein the tumor is a mesothelioma, a lung tumor, a breast tumor, a head and neck squamous carcinoma, a colon tumor, a pancreatic tumor, a prostate tumor, or a liver carcinoma.
16 . The antibody conjugate of claim 15 , wherein the cancer drug is monomethyl auristin E (MMAE).
17 . A pharmaceutical composition, comprising the antibody-drug conjugate of claim 14 and a pharmaceutical carrier.
18 . A method of treating a tumor in a subject, comprising:
administering the pharmaceutical composition of claim 17 to a subject in need thereof, wherein the tumor expresses hNTSR1.
19 . The method of claim 18 , wherein the tumor is a mesothelioma, lung tumor, breast tumor, head and neck squamous carcinoma, colon tumor, pancreatic tumor, prostate tumor, or liver carcinoma.
20 . A method of detecting hNTSR1, comprising:
contacting a sample, tissue or cell with the antibody of claim 1 or the antibody conjugate of claim 12 ; and
determining binding of the antibody or antibody conjugate to a target in the sample, or to the tissue or cell.
21 . The method of claim 20 , wherein the antibody conjugate includes a detectable label.