Drug complex for treatment of metastatic prostate cancer

Abstract

A drug complex for delivery of a drug or other agent to a target cell, comprising a targeting carrier molecule which is selectively distributed to a specific cell type or tissue containing the specific cell type; a linker which is acted upon by a molecule which is present at an effective concentration in the environs of the specific cell type; and a drug or an agent to be delivered to the specific cell type. In particular, a drug complex for delivering a cytotoxic drug to prostate cancer cells, comprising a targeting carrier molecule which is selectively delivered to prostate tissue, bone or both; a peptide which is a substrate for prostate specific antigen; and a cytotoxic drug which is toxic to androgen independent prostate cancer cells.

We claim:  
     
         1 . A drug complex comprising: 
 a) a targeting carrier molecule which, when introduced into an individual, is selectively distributed to a specific cell type or tissue containing the specific cell type;    b) a linker which is acted upon by a molecule present at an effective concentration in the environs of the specific cell type; and    c) a drug or an agent to be delivered to the specific cell type.    
     
     
         2 . A drug complex comprising: 
 a) a targeting carrier molecule which, when introduced into an individual, is selectively delivered to prostate tissue, bone or both;    b) a peptide which is a substrate for prostate specific antigen; and    c) a cytotoxic drug which is toxic to androgen independent prostate cancer cells,    wherein the peptide links the targeting molecule and the cytotoxic drug.    
     
     
         3 . The drug complex of  claim 2 , wherein the targeting carrier molecule is selected from the group consisting of polyamines; the peptide linker is selected from the group consisting of SEQ ID NOS. 1-14 and alanine-lysine-phenylalanine-glutamate; and the cytotoxic drug is selected from the group consisting of: adriamycin, amonafide, cisplatin, carboplatin (CBDCA), CHIP, cyclophosphamide, doxorubicin, epirubicin, estramustine, etoposide, 5-fluorouracil, gallium nitrate, idarubicin, ifosfamide+mesna, ketoconazole, liarozole (R85,246), methotrexate, mitomycin C, mitoguazone, mitoxantrone, proscar (finasteride), suramin, taxol, thapsigargin, trimetrexate, vinblastine (CI), and vinblastine and emcyt.  
     
     
         4 . The drug complex of  claim 3 , wherein the polyamine is selected from the group consisting of putrescine, spermine, and spermidine.  
     
     
         5 . The drug complex of  claim 4 , wherein the putrescine is fluoropropylputrescine.  
     
     
         6 . The drug complex of  claim 2 , wherein the peptide linker additionally comprises a chemical selected from the group consisting of para-amino benzoic acid and para-aminobenzyloxycarbonyl.  
     
     
         7 . A method of killing androgen independent prostate cancer cells in a man with prostate cancer, comprising administering to the man a therapeutically effective amount of a drug complex which comprises: 
 a) a targeting carrier molecule which is selectively delivered to prostate tissue and bone;    b) a peptide which is a substrate for prostate specific antigen; and    c) a cytotoxic drug which is toxic to androgen independent prostate cancer cells,    wherein the peptide links the targeting molecule and the cytotoxic drug and wherein the drug complex is administered to the man in such a manner that it is delivered to androgen independent prostate cancer cells and the cytotoxic drug enters androgen independent prostate cancer cells, thereby killing the cells.    
     
     
         8 . The method of  claim 7 , wherein the peptide which is a substrate for prostate specific antigen is selected from the group consisting of SEQ ID NOS. 1-14 and alanine-lysine-phenylalanine-glutamate.  
     
     
         9 . The method of  claim 7 , wherein the targeting carrier molecule is selected from the group consisting of polyamines.  
     
     
         10 . The method of  claim 9 , wherein the polyamine is selected from the group consisting of putrescine, spermine, and spermidine.  
     
     
         11 . The method of  claim 10 , wherein the putrescine is fluoropropylputrescine.  
     
     
         12 . The method of  claim 7 , wherein the peptide linker additionally comprises a chemical selected from the group consisting of para-amino benzoic acid and para-aminobenzyloxycarbonyl.  
     
     
         13 . The method of  claim 12 , wherein the drug complex is administered intravenously.  
     
     
         14 . The method of  claim 13 , wherein the cytotoxic drug is selected from the group consisting of: adriamycin, amonafide, cisplatin, carboplatin (CBDCA), CHIP, cyclophosphamide, doxorubicin, epirubicin, estramustine, etoposide, 5-fluorouracil, gallium nitrate, idarubicin, ifosfamide+mesna, ketoconazole, liarozole (R85,246), methotrexate, mitomycin C, mitoguazone, mitoxantrone, proscar (finasteride), suramin, taxol, thapsigargin, trimetrexate, vinblastine (CI), and vinblastine and emcyt.  
     
     
         15 . A method of treating metastatic prostate cancer in an man, comprising administering to the man a therapeutically effective amount of a drug complex which comprises: 
 a) a targeting carrier molecule which is selectively delivered to prostate tissue and bone;    b) a peptide which is a substrate for prostate specific antigen; and    c) a cytotoxic drug which is toxic to metastatic prostate cancer cells,    wherein the peptide links the targeting molecule and the cytotoxic drug and wherein the drug complex is administered to the man in such a manner that it is delivered to prostate tissue and bone and the cytotoxic drug enters metastatic prostate cancer cells, thereby killing the cells.    
     
     
         16 . The method of  claim 15 , wherein the peptide which is a substrate for prostate specific antigen is selected from the group consisting of SEQ ID NOS. 1-14 and alanine-lysine-phenylalanine-glutamate.  
     
     
         17 . The method of  claim 15 , wherein the targeting carrier molecule is selected from the group consisting of polyamines.  
     
     
         18 . The method of  claim 17 , wherein the polyamine is selected from the group consisting of putrescine, spermine, and spermidine.  
     
     
         19 . The method of  claim 18 , wherein the putrescine is fluoropropylputrescine.  
     
     
         20 . The method of  claim 15 , wherein the peptide linker additionally comprises a chemical selected from the group consisting of para-amino benzoic acid and para-aminobenzyloxycarbonyl.  
     
     
         21 . The method of  claim 20 , wherein the drug complex is administered intravenously.  
     
     
         22 . The method of  claim 21 , wherein the cytotoxic drug is selected from the group consisting of: adriamycin, amonafide, cisplatin, carboplatin (CBDCA), CHIP, cyclophosphamide, doxorubicin, epirubicin, estramustine, etoposide, 5-fluorouracil, gallium nitrate, idarubicin, ifosfamide+mesna, ketoconazole, liarozole (R85,246), methotrexate, mitomycin C, mitoguazone, mitoxantrone, proscar (finasteride), suramin, taxol, thapsigargin, trimetrexate, vinblastine (CI), and vinblastine and emcyt.