Fully human antibodies specific to cadm1

Abstract

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.

What is claimed: 
     
         1 . An isolated monoclonal antibody, or an antigen-binding portion thereof, which binds to an epitope on human CADM1 recognized by a second antibody, wherein the second antibody comprises heavy and light chain variable regions comprising the amino acid sequences set forth in SEQ ID NOs:19 and 22, respectively. 
     
     
         2 . An isolated monoclonal antibody, or an antigen-binding portion thereof, which binds to an epitope on human CADM1 recognized by a second antibody, wherein the second antibody comprises heavy and light chain variable regions comprising the amino acid sequences set forth in SEQ ID NOs:20 and 23, respectively. 
     
     
         3 . An isolated monoclonal antibody, or an antigen-binding portion thereof, which binds to an epitope on human CADM1 recognized by a second antibody, wherein the second antibody comprises heavy and light chain variable regions comprising the amino acid sequences set forth in SEQ ID NOs:21 and 24, respectively. 
     
     
         4 . The monoclonal antibody, or an antigen-binding portion thereof, of  claim 1 , which is conjugated to a therapeutic agent. 
     
     
         5 . The monoclonal antibody, or an antigen-binding portion thereof, of  claim 2 , which is conjugated to a therapeutic agent. 
     
     
         6 . The monoclonal antibody, or an antigen-binding portion thereof, of  claim 3 , which is conjugated to a therapeutic agent. 
     
     
         7 . A composition comprising the monoclonal antibody, or an antigen-binding portion thereof, of  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         8 . A composition comprising the monoclonal antibody, or an antigen-binding portion thereof, of  claim 2  and a pharmaceutically acceptable carrier. 
     
     
         9 . A composition comprising the monoclonal antibody, or an antigen-binding portion thereof, of  claim 3  and a pharmaceutically acceptable carrier. 
     
     
         10 . A method for treating a disease associated with target cells expressing CADM1 comprising administering to a subject the monoclonal antibody, or an antigen-binding portion thereof, of  claim 1  in an amount effective to treat the disease. 
     
     
         11 . A method for treating a disease associated with target cells expressing CADM1 comprising administering to a subject the monoclonal antibody, or an antigen-binding portion thereof, of  claim 2  in an amount effective to treat the disease. 
     
     
         12 . A method for treating a disease associated with target cells expressing CADM1 comprising administering to a subject the monoclonal antibody, or an antigen-binding portion thereof, of  claim 3  in an amount effective to treat the disease. 
     
     
         13 . The method of  claim 10 , wherein the disease is a human cancer 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. 
     
     
         14 . The method of  claim 11 , wherein the disease is a human cancer 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. 
     
     
         15 . The method of  claim 12 , wherein the disease is a human cancer 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. 
     
     
         16 . An isolated monoclonal antibody, or antigen binding portion thereof, comprising a heavy chain variable region and a light chain variable region, wherein:
 the heavy chain variable region comprises an amino acid sequence that is at least 80% homologous to an amino acid sequence selected from the group consisting of SEQ ID NOs: 19, 20, and 21;   the light chain variable region comprises an amino acid sequence that is at least 80% homologous to an amino acid sequence selected from the group consisting of SEQ ID NOs: 22, 23 and 24;   and the antibody binds to human CADM1 with a EC 50  of 10 nM or less.   
     
     
         17 . The monoclonal antibody, or an antigen-binding portion thereof, of  claim 16 , which is conjugated to a therapeutic agent. 
     
     
         18 . A composition comprising the monoclonal antibody, or an antigen-binding portion thereof, of  claim 16  and a pharmaceutically acceptable carrier. 
     
     
         19 . A method for treating a disease associated with target cells expressing CADM1 comprising administering to a subject the monoclonal antibody, or an antigen-binding portion thereof, of  claim 16  in an amount effective to treat the disease. 
     
     
         20 . The method of  claim 19 , wherein the disease is a human cancer 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.