Anti-alpha-v integrin antibody for the treatment of prostate cancer

Abstract

The invention is directed to the treatment of prostate cancer by means of antibodies. Above all, the invention relates to the administration of an anti-alpha-v integrin (receptor) antibody to patients suffering from prostate cancer, especially castration-resistant prostate cancer (CRPC), optionally accompanied by lymph node and bone tissue metastases (mCRPC). In particular, the invention relates to the therapy of said patients by means of the anti-angiogenic antibody DI17E6 and structural mutants thereof.

1 . A method of treating a patient suffering from castrate-resistant prostate cancer (CRPC), the method comprising administering to the patient an anti-alpha integrin antibody in an amount of 500 mg or higher per two weeks for 4-8 months, or 1000 mg or higher per month for 4-8 months, wherein the antibody comprises:
 a light chain comprising a variable region having an amino acid sequence having at least 95% sequence identity with the variable region amino acid sequence of SEQ ID NO:1, and a constant region having an amino acid sequence having at least 98% sequence identity with the constant region amino acid sequence of SEQ ID NO:1, and   
       a heavy chain comprising a variable region having an amino acid sequence having at least 95% sequence identity with the variable region amino acid sequence of SEQ ID NO:2, and a constant region having an amino acid sequence having at least 98% sequence identity with the constant region amino acid sequence of SEQ ID NO:2. 
     
     
         2 . The method of  claim 1 , wherein the cancer is metastasizing. 
     
     
         3 . The method of  claim 2 , wherein the cancer is associated with lymph node metastases. 
     
     
         4 . The method of  claim 2 , wherein the cancer is associated with bone metastases. 
     
     
         5 . (canceled) 
     
     
         6 . The method of  claim 1 , wherein the patient experiences a reduction in a prostate specific antigen (PSA) value within 4-6 months of starting treatment. 
     
     
         7 . The method of  claim 1 , wherein the number of circulating tumor cells (CTC) declines during antibody treatment. 
     
     
         8 . The method of  claim 1 , wherein the patient's prostate was removed before treatment. 
     
     
         9 . The method of  claim 1 , wherein the patient was pretreated with chemotherapeutics and/or radiation. 
     
     
         10 - 11 . (canceled) 
     
     
         12 . The method of  claim 1 , wherein the antibody is administered as monotherapy. 
     
     
         13 . (canceled) 
     
     
         14 . The method of  claim 1 , wherein the antibody comprises a modification to one or more amino acids within the heavy chain framework regions corresponding to A9, E13, M20, K38, R40, A72, S76, Q82, G85, T87, S91, or S113 or SEQ ID NO:2. 
     
     
         15 - 16 . (canceled) 
     
     
         17 . The method of  claim 1 , wherein the patient's CRPC is progressive after chemotherapy. 
     
     
         18 . The method of  claim 1 , wherein the patient is treated after prostatectomy or other prostate cancer related surgery or radiotherapy. 
     
     
         19 . The method of  claim 1 , wherein the method comprises a sequential or simultaneous administration with an hormonal agent. 
     
     
         20 . The method of  claim 1 , wherein the method comprises sequential or simultaneous administration with a cytostatic or cytotoxic agent selected from the group consisting of a chemotherapeutic agent, radiation, a tyrosine kinase inhibitor, and an angiogenesis inhibitor. 
     
     
         21 . The method of  claim 20 , wherein said tyrosine kinase inhibitor is an anti-ErbB antibody selected from the group consisting of an anti-EGFR antibody, an anti-Her2 antibody, and an anti-Her3 antibody, and said angiogenesis inhibitor is an alpha-v integrin inhibitor. 
     
     
         22 - 27 . (canceled) 
     
     
         28 . The method of  claim 1 , wherein the antibody comprises a light chain comprising the amino acid sequence of SEQ ID NO:1 and a heavy chain comprising the amino acid sequence of SEQ ID NO:2, wherein the antibody is administered to said patient in an amount of 1000-2000 mg per month. 
     
     
         29 . The method of  claim 1 , wherein the antibody is administered to said patient in an amount of 500-1000 mg per two weeks or 1000-2000 mg per month.