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 . The anti-av integrin antibody DI17E6 or a biologically active variant or modification thereof, for use in the treatment of patients suffering from castrate-resistant prostate cancer (CRPC). 
     
     
         2 . DI17E6 antibody of  claim 1 , wherein the cancer is metastasizing. 
     
     
         3 . DI17E6 antibody of  claim 2 , wherein the cancer is associated with lymph node metastases. 
     
     
         4 . DI17E6 antibody of  claim 2 , wherein the cancer is associated with bone metastases. 
     
     
         5 . (canceled) 
     
     
         6 . DI17E6 antibody of  claim 1 , wherein the reduction of the PSA value was achieved within 4-6 months of treatment. 
     
     
         7 . DI17E6 antibody of  claim 1 , wherein the number of the circulating tumor cells (CTC) is declined during antibody treatment. 
     
     
         8 . DI17E6 antibody of  claim 1 , wherein the patient's prostate was removed before treatment. 
     
     
         9 . DI17E6 antibody of  claim 1 , wherein the patient was pretreated with chemotherapeutics and/or radiation. 
     
     
         10 . DI17E6 antibody of  claim 1 , wherein the effective dose of the antibody is 500 mg-1000 mg per two weeks. 
     
     
         11 . (canceled) 
     
     
         12 . DI17E6 antibody of  claim 1 , wherein the antibody is administered as monotherapy. 
     
     
         13 . DI17E6 antibody of  claim 1 , wherein the biological active variant or modification comprises the CDR regions and heavy and light chain variable regions of DI17E6, which are at least 80% identical in amino acid sequence compared to the variable regions of DI17E6. 
     
     
         14 . The DI17E6 antibody of  claim 13 , comprising one or more modifications within the heavy chain framework regions
 FR1: QVQLQQSG A ELA E PGASVK M SCKASGYTFS (SEQ ID No. 16)   FR2: WV K Q R PGQGLEWIG (SEQ ID No. 17)   FR3: KATMT A DTS S STAYM Q LS G L T SED S AVYYCAS (SEQ ID No. 18)   FR4: WGQGT S VTVSS (SEQ ID No. 19),   wherein one or more of the bold and underlined positions are mutated   and are different compared to the original respective sequence.   
     
     
         15 . DI17E6 antibody of  claim 1 , wherein the biological active variant or modification comprises a constant region, which is at least 80% identical in amino acid sequence compared to the constant region of DI17E6. 
     
     
         16 . (canceled) 
     
     
         17 . DI17E6 antibody of  claim 1 , wherein the patient's CRPC is progressive after chemotherapy. 
     
     
         18 . DI17E6 antibody of  claim 1 , wherein the patient is treated after prostatectomy or other prostate cancer related surgery or radiotherapy. 
     
     
         19 . DI17E6 antibody of  claim 1 , wherein the antibody treatment comprises a sequential or simultaneous administration with an hormonal agent. 
     
     
         20 . DI17E6 antibody of  claim 1 , wherein the antibody treatment comprises sequential or simultaneous administration with an cytostatic or cytotoxic agent selected from the group consisting of: a chemotherapeutic agent, radiation, a tyrosine kinase inhibitor, and an angiogenesis inhibitor. 
     
     
         21 . DI17E6 antibody 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 - 25 . (canceled) 
     
     
         26 . The anti-av integrin antibody DI17E6 or a biologically active variant, or modification thereof for use of reducing pain occurring in CRPC accompanied by bone and/or lymph node metastasis, wherein the effective dose of the antibody is 500-1500 mg administered each two weeks. 
     
     
         27 . (canceled)