Cancer therapy using cldn6 target-directed antibodies in vivo

Abstract

The invention relates to the treatment and/or prevention of tumor diseases associated with cells expressing CLDN6, in particular cancer and cancer metastasis using antibodies which bind to CLDN6. The present application demonstrates that the binding of antibodies to CLDN6 on the surface of tumor cells is sufficient to inhibit growth of the tumor and to prolong survival and extend the lifespan of tumor patients. Furthermore, binding of antibodies to CLDN6 is efficient in inhibiting growth of CLDN6 positive germ cell tumors such as teratocarcinomas or embryonal carcinomas, in particular germ cell tumors of the testis.

1 . An antibody which inhibits growth of a tumor in vivo, wherein the cells of the tumor express claudin 6 (CLDN6) and wherein the antibody is capable of binding to CLDN6. 
     
     
         2 . The antibody of  claim 1 , wherein the antibody inhibits growth of the tumor by binding to CLDN6. 
     
     
         3 . The antibody of  claim 1  or  2 , wherein the antibody is specific for CLDN6. 
     
     
         4 . The antibody of any one of  claims 1  to  3 , wherein the antibody is a monoclonal, chimeric, human or humanized antibody, or is a fragment of an antibody or a synthetic antibody. 
     
     
         5 . The antibody of any one of  claims 1  to  4 , wherein the tumor is selected from the group consisting of ovarian cancer, in particular ovarian adenocarcinoma and ovarian teratocarcinoma, lung cancer, including small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), in particular squamous cell lung carcinoma and adenocarcinoma, gastric cancer, breast cancer, hepatic cancer, pancreatic cancer, skin cancer, in particular basal cell carcinoma and squamous cell carcinoma, malignant melanoma, head and neck cancer, in particular malignant pleomorphic adenoma, sarcoma, in particular synovial sarcoma and carcinosarcoma, bile duct cancer, cancer of the urinary bladder, in particular transitional cell carcinoma and papillary carcinoma, kidney cancer, in particular renal cell carcinoma including clear cell renal cell carcinoma and papillary renal cell carcinoma, colon cancer, small bowel cancer, including cancer of the ileum, in particular small bowel adenocarcinoma and adenocarcinoma of the ileum, testicular embryonal carcinoma, placental choriocarcinoma, cervical cancer, testicular cancer, in particular testicular seminoma, testicular teratoma and embryonic testicular cancer, uterine cancer, a germ cell tumor, in particular a teratocarcinoma or an embryonal carcinoma, preferably a germ cell tumor of the testis, and the metastatic forms thereof. 
     
     
         6 . An antibody selected from the group consisting of:
 (i) an antibody produced by or obtainable from a clone deposited under the accession no. DSM ACC3059 (GT512muMAB 36A), DSM ACC3058 (GT512muMAB 27A), or DSM ACC3057 (GT512muMAB 5F2D2),   (ii) an antibody which is a chimerized or humanized form of the antibody under (i),   (iii) an antibody which has the specificity of the antibody under (i), and   (iv) an antibody comprising the antigen binding portion or antigen binding site of the antibody under (i),   wherein the antigen binding portion or antigen binding site of the antibody under (i) preferably comprises the variable region of the antibody under (i).   
     
     
         7 . The antibody of any one of  claims 1  to  6  attached to at least one therapeutic effector moiety, wherein the therapeutic effector moiety preferably is a radiolabel, cytotoxin or cytotoxic enzyme. 
     
     
         8 . A hybridoma capable of producing the antibody of any one of  claims 1  to  7 . 
     
     
         9 . A hybridoma deposited under the accession no. DSM ACC3059 (GT512muMAB 36A), DSM ACC3058 (GT512muMAB 27A), or DSM ACC3057 (GT512muMAB 5F2D2). 
     
     
         10 . A pharmaceutical composition comprising the antibody of any one of  claims 1  to  7 , wherein the pharmaceutical composition preferably is in the form of a therapeutic or prophylactic tumor vaccine. 
     
     
         11 . The pharmaceutical composition of  claim 10  for use in treating or preventing a tumor disease. 
     
     
         12 . A method of treating a patient having a tumor disease or being at risk of developing a tumor disease, wherein the cells of the tumor express claudin 6 (CLDN6) and wherein the method comprises the administration of an antibody capable of binding to CLDN6. 
     
     
         13 . The method of  claim 12 , wherein the antibody when administered to the patient inhibits growth of the tumor in the patient by binding to CLDN6. 
     
     
         14 . The method of  claim 12  or  13 , wherein the antibody is attached to at least one therapeutic effector moiety, wherein the therapeutic effector moiety preferably is a radiolabel, cytotoxin or cytotoxic enzyme. 
     
     
         15 . The method of any one of  claims 12  to  14 , wherein the antibody is specific for CLDN6. 
     
     
         16 . The method of any one of  claims 12  to  15 , wherein the antibody is a monoclonal, chimeric, human or humanized antibody, or is a fragment of an antibody or a synthetic antibody. 
     
     
         17 . The method of any one of  claims 12  to  16 , wherein the method comprises the administration of a pharmaceutical composition of  claim 10  or  11 . 
     
     
         18 . The pharmaceutical composition of  claim 11  or the method of any one of  claims 12  to  17 , wherein the tumor disease is selected from the group consisting of ovarian cancer, in particular ovarian adenocarcinoma and ovarian teratocarcinoma, lung cancer, including small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), in particular squamous cell lung carcinoma and adenocarcinoma, gastric cancer, breast cancer, hepatic cancer, pancreatic cancer, skin cancer, in particular basal cell carcinoma and squamous cell carcinoma, malignant melanoma, head and neck cancer, in particular malignant pleomorphic adenoma, sarcoma, in particular synovial sarcoma and carcinosarcoma, bile duct cancer, cancer of the urinary bladder, in particular transitional cell carcinoma and papillary carcinoma, kidney cancer, in particular renal cell carcinoma including clear cell renal cell carcinoma and papillary renal cell carcinoma, colon cancer, small bowel cancer, including cancer of the ileum, in particular small bowel adenocarcinoma and adenocarcinoma of the ileum, testicular embryonal carcinoma, placental choriocarcinoma, cervical cancer, testicular cancer, in particular testicular seminoma, testicular teratoma and embryonic testicular cancer, uterine cancer, a germ cell tumor disease, in particular a teratocarcinoma or an embryonal carcinoma, preferably a germ cell tumor disease of the testis, and the metastatic forms thereof. 
     
     
         19 . The antibody of any one of  claims 1  to  7 , the pharmaceutical composition of any one of  claims 10 ,  11  and  18  or the method of any one of  claims 12  to  18 , wherein CLDN6 comprises an amino acid sequence encoded by a nucleic acid which comprises the nucleic acid sequence according to SEQ ID NO: 1 of the sequence listing or a variant of said nucleic acid sequence. 
     
     
         20 . The antibody of any one of  claims 1  to  7  and  19 , the pharmaceutical composition of any one of  claims 10 ,  11 ,  18  and  19  or the method of any one of  claims 12  to  19 , wherein CLDN6 comprises the amino acid sequence according to SEQ ID NO: 2 of the sequence listing or a variant of said amino acid sequence.