Fully human antibodies specific to CADM1
View Patent ↗The present disclosure provides isolated monoclonal antibodies, particularly human monoclonal antibodies, more particularly engineered antibodies resulting in increased binding to Fc receptors and/or increased potency for ADCC or immunoconjugates, which specifically bind to CADM1 with high affinity. Nucleic acid molecules encoding CADM1 antibodies, expression vectors, host cells and methods for expressing the CADM1 antibodies are also provided. Bispecific molecules and pharmaceutical compositions comprising the CADM1 antibodies are also provided. Methods for detecting CADM1, as well as methods for treating various cancers, including lung cancer and pancreatic cancer, are disclosed.
1. An isolated monoclonal antibody, or an antigen-binding portion thereof, which binds human CADM1 and which comprises heavy and light chain variable regions, wherein the regions are selected from the group consisting of:
(a) a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO:19, 20, or 21;
(b) a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO:22, 23, or 24;
(c) a heavy chain variable region CDR1 comprising SEQ ID NO:1, a heavy chain variable region CDR2 comprising SEQ ID NO:4, a heavy chain variable region CDR3 comprising SEQ ID NO:7, a light chain variable region CDR1 comprising SEQ ID NO:10, a light chain variable region CDR2 comprising SEQ ID NO:13 and a light chain variable region CDR3 comprising SEQ ID NO:16;
(d) a heavy chain variable region CDR1 comprising SEQ ID NO:2, a heavy chain variable region CDR2 comprising SEQ ID NO:5, a heavy chain variable region CDR3 comprising SEQ ID NO:8, a light chain variable region CDR1 comprising SEQ ID NO:11, a light chain variable region CDR2 comprising SEQ ID NO:14 and a light chain variable region CDR3 comprising SEQ ID NO:17;
(e) a heavy chain variable region CDR1 comprising SEQ ID NO:3, a heavy chain variable region CDR2 comprising SEQ ID NO:6, a heavy chain variable region CDR3 comprising SEQ ID NO:9, a light chain variable region CDR1 comprising SEQ ID NO:12, a light chain variable region CDR2 comprising SEQ ID NO:15 and a light chain variable region CDR3 comprising SEQ ID NO:18;
(f) heavy and light chain variable regions comprising the amino acid sequences set forth in SEQ ID NOs:19 and 22, respectively;
(g) heavy and light chain variable regions comprising the amino acid sequences set forth in SEQ ID NOs:20 and 23, respectively; and
(h) heavy and light chain variable regions comprising the amino acid sequences set forth in SEQ ID NOs:21 and 24, respectively.
2. The antibody of claim 1 , wherein said antibody is a full-length antibody of an IgG1, IgG2, IgG3, or IgG4 isotype.
3. The antibody of claim 1 , wherein said antibody is selected from the group consisting of: a whole antibody, an antibody fragment, a humanized antibody, a human antibody, a single chain antibody, an engineered antibody resulting in increased binding to Fc receptors and/or increased potency for ADCC, and a bispecific antibody.
4. The antibody of claim 1 which is conjugated to a therapeutic agent.
5. The antibody of claim 4 wherein the therapeutic agent is a cytotoxin or a radioactive isotope.
6. The isolated antibody of claim 1 , wherein said antibody binds to human CADM1 with an EC 50 in the range of <50 nM, <10 nM, or <1 nM.
7. A composition comprising the isolated antibody or antigen-binding portion thereof of claim 1 and a pharmaceutically acceptable carrier.
8. A hybridoma expressing the antibody or antigen binding portion thereof of claim 1 .
9. The isolated monoclonal antibody, or an antigen-binding portion thereof, of claim 1 , comprising a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO:19.
10. The isolated monoclonal antibody, or an antigen-binding portion thereof, of claim 1 , comprising a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO:20.
11. The isolated monoclonal antibody, or an antigen-binding portion thereof, of claim 1 , comprising a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO:21.
12. The isolated monoclonal antibody, or an antigen-binding portion thereof, of claim 1 , comprising a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO:22.
13. The isolated monoclonal antibody, or an antigen-binding portion thereof, of claim 1 , comprising a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO:23.
14. The isolated monoclonal antibody, or an antigen-binding portion thereof, of claim 1 , comprising a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO:24.
15. The isolated monoclonal antibody, or an antigen-binding portion thereof, of claim 1 , comprising a heavy chain variable region CDR1 comprising SEQ ID NO:1, a heavy chain variable region CDR2 comprising SEQ ID NO:4, a heavy chain variable region CDR3 comprising SEQ ID NO:7, a light chain variable region CDR1 comprising SEQ ID NO:10, a light chain variable region CDR2 comprising SEQ ID NO:13 and a light chain variable region CDR3 comprising SEQ ID NO:16.
16. The isolated monoclonal antibody, or an antigen-binding portion thereof, of claim 1 , comprising a heavy chain variable region CDR1 comprising SEQ ID NO:2, a heavy chain variable region CDR2 comprising SEQ ID NO:5, a heavy chain variable region CDR3 comprising SEQ ID NO:8, a light chain variable region CDR1 comprising SEQ ID NO:11, a light chain variable region CDR2 comprising SEQ ID NO:14 and a light chain variable region CDR3 comprising SEQ ID NO:17.
17. The isolated monoclonal antibody, or an antigen-binding portion thereof, of claim 1 , comprising a heavy chain variable region CDR1 comprising SEQ ID NO:3, a heavy chain variable region CDR2 comprising SEQ ID NO:6, a heavy chain variable region CDR3 comprising SEQ ID NO:9, a light chain variable region CDR1 comprising SEQ ID NO:12, a light chain variable region CDR2 comprising SEQ ID NO:15 and a light chain variable region CDR3 comprising SEQ ID NO:18.
18. The isolated monoclonal antibody, or an antigen-binding portion thereof, of claim 1 , comprising heavy and light chain variable regions comprising the amino acid sequences set forth in SEQ ID NOs:19 and 22, respectively.
19. The isolated monoclonal antibody, or an antigen-binding portion thereof, of claim 1 , comprising heavy and light chain variable regions comprising the amino acid sequences set forth in SEQ ID NOs:20 and 23, respectively.
20. The isolated monoclonal antibody, or an antigen-binding portion thereof, of claim 1 , comprising heavy and light chain variable regions comprising the amino acid sequences set forth in SEQ ID NOs:21 and 24, respectively.
21. A method for treating a disease associated with target cells expressing CADM1, wherein the disease associated with target cells expressing CADM1 is a cancer, said method comprising the step of administering to a subject the anti-CADM1 antibody, or antigen-binding portion thereof, of claim 1 , wherein said antibody or antigen-binding portion thereof is conjugated to a therapeutic agent, in an amount effective to treat the disease.
22. The method of claim 21 , wherein said cancer is selected from the group consisting of: small cell lung cancer, adult T-cell leukemia, non-small cell lung cancer (including squamous carcinomas and adenocarcinomas), melanoma, breast cancer, colorectal cancer, ovarian cancer, prostate cancer, neuroendocrine cancers including those of lung, adrenal, pituitary, GI-tract, kidney, liver (including hepatocellular carcinomas), pancreas (including insulinomas and glucagonomas), glioblastomas, and carcinoid tumors including those of the pancreas, lung, GI tract, liver, and kidney.