Compounds for immunotherapy of prostate cancer and methods for their use

Abstract

Compounds and methods for treating prostate cancer are provided. The inventive compounds include polypeptides containing at least a portion of a prostate tumor protein. Vaccines and pharmaceutical compositions for immunotherapy of prostate cancer comprising such polypeptides, or DNA molecules encoding such polypeptides, are also provided, together with DNA molecules for preparing the inventive polypeptides.

1 . An isolated polypeptide comprising an immunogenic portion of a prostate protein or a variant thereof, wherein said protein comprises an amino acid sequence encoded by a DNA molecule having a sequence selected from the group consisting of nucleotide sequences recited in SEQ ID NOS: 2, 3, 8-29, 41-45, 47-52, 54-65, 70, 73-74, 79, 81, 87, 90, 92, 93, 97, 103, 104, 107, 109-111, 115-160, 171, 173-175, 177, 181, 188, 191, 193, 194, 198, 203, 204, 207, 209, 220, 222-225, 227 and 228, the complements of said nucleotide sequences and sequences that hybridize to a nucleotide sequence of SEQ ID NOS: 2, 3, 8-29, 41-45, 47-52, 54-65, 70, 73-74, 79, 81, 87, 90, 92, 93, 97, 103, 104, 107, 109-111, 115-160, 171, 173-175, 177, 181, 188, 191, 193, 194, 198, 203, 204, 207, 209, 220, 222-225, 227 and 228 under moderately stringent conditions.  
     
     
         2 . An isolated DNA molecule comprising a nucleotide sequence encoding the polypeptide of  claim 1 .  
     
     
         3 . An isolated DNA molecule having a sequence provided in SEQ ID NOS: 2, 3, 8-29, 41-45, 47-52, 54-65, 70, 73-74, 79, 81, 87, 90, 92, 93, 97, 103, 104, 107, 109-111, 115-160, 171, 173-175, 177, 181, 188, 191, 193, 194, 198, 203, 204, 207, 209, 220, 222-225, 227 or 228.  
     
     
         4 . An expression vector comprising the DNA molecule of claims  2  or  3 .  
     
     
         5 . A host cell transformed with the expression vector of  claim 4 .  
     
     
         6 . The host cell of  claim 5  wherein the host cell is selected from the group consisting of  E. coli , yeast and mammalian cell lines.  
     
     
         7 . A pharmaceutical composition comprising the polypeptide of  claim 1  and a physiologically acceptable carrier.  
     
     
         8 . A vaccine comprising the polypeptide of  claim 1  and a non-specific immune response enhancer.  
     
     
         9 . The vaccine of  claim 8  wherein the non-specific immune response enhancer is an adjuvant.  
     
     
         10 . A vaccine comprising the DNA molecule of claims  2  or  3  and a non-specific immune response enhancer.  
     
     
         11 . The vaccine of  claim 10  wherein the non-specific immune response enhancer is an adjuvant.  
     
     
         12 . A pharmaceutical composition for the treatment of prostate cancer comprising a polypeptide and a physiologically acceptable carrier, the polypeptide comprising an immunogenic portion of a prostate protein or of a variant thereof, wherein said protein comprises an amino acid sequence encoded by a DNA molecule having a sequence selected from the group consisting of nucleotide sequences recited in SEQ ID NOS: 5-7, 30-40, 46, 53, 66-69, 71, 72, 75-78, 80, 82-86, 88, 89, 91, 94-96, 98-102, 105, 106, 161-170, 179, 180, 182-187, 189, 190, 192, 195-197, 199-202, 205, 206, 208, 212-219, 221 and 226, the complements of said nucleotide sequences and sequences that hybridize to a sequence of SEQ ID NOS: 5-7, 30-40, 46, 53, 66-69, 71, 72, 75-78, 80, 82-86, 88, 89, 91, 94-96, 98-102, 105, 106, 161-170, 179, 180, 182-187, 189, 190, 192, 195-197, 199-202, 205, 206, 208, 212-219, 221 or 226 under moderately stringent conditions.  
     
     
         13 . A vaccine for the treatment of prostate cancer comprising a polypeptide and a non-specific immune response enhancer, said polypeptide comprising an immunogenic portion of a prostate protein or a variant thereof, wherein said protein comprises an amino acid sequence encoded by a DNA molecule having a sequence selected from the group consisting of nucleotide sequences recited in SEQ ID NOS: 5-7, 30-40, 46, 53, 66-69, 71, 72, 75-78, 80, 82-86, 88, 89, 91, 94-96, 98-102, 105, 106, 161-170, 179, 180, 182-187, 189, 190, 192, 195-197, 199-202, 205, 206, 208, 212-219, 221 and 226, the complements of said nucleotide sequences and sequences that hybridize to a sequence of SEQ ID NOS: 5-7, 30-40, 46, 53, 66-69, 71, 72, 75-78, 80, 82-86, 88, 89, 91, 94-96, 98-102, 105, 106, 161-170, 179, 180, 182-187, 189, 190, 192, 195-197, 199-202, 205, 206, 208, 212-219, 221 or 226 under moderately stringent conditions.  
     
     
         14 . The vaccine of  claim 13  wherein the non-specific immune response enhancer is an adjuvant.  
     
     
         15 . A vaccine for the treatment of prostate cancer comprising a DNA molecule and a non-specific immune response enhancer, the DNA molecule having a sequence selected from the group consisting of nucleotide sequences recited in SEQ ID NOS: 5-7, 30-40, 46, 53, 66-69, 71, 72, 75-78, 80, 82-86, 88, 89, 91, 94-96, 98-102, 105, 106, 161 170, 179, 180, 182-187, 189, 190, 192, 195-197, 199-202, 205, 206, 208, 212-219, 221 and 226, the complements of said nucleotide sequences and sequences that hybridize to a sequence of SEQ ID NOS: 5-7, 30-40, 46, 53, 66-69, 71, 72, 75-78, 80, 82-86, 88, 89, 91, 94-96, 98-102, 105, 106, 161-170, 179, 180, 182-187, 189, 190, 192, 195-197, 199-202, 205, 206, 208, 212-219, 221 or 226 under moderately stringent conditions.  
     
     
         16 . The vaccine of  claim 15 , wherein the non-specific immune response enhancer is an adjuvant.  
     
     
         17 . A method for inhibiting the development of prostate cancer in a patient, comprising administering to the patient an effective amount of the pharmaceutical composition of claims  7  or  12 .  
     
     
         18 . A method for inhibiting the development of prostate cancer in a patient, comprising administering to the patient an effective amount of the vaccine of any one of claims  8 ,  10 ,  13  or  15 .  
     
     
         19 . A fusion protein comprising at least one polypeptides according to  claim 1 .  
     
     
         20 . A fusion protein comprising a polypeptide according to  claim 1  and a known prostate antigen.  
     
     
         21 . A pharmaceutical composition comprising a fusion protein according to any one of claims  19 - 20  and a physiologically acceptable carrier.  
     
     
         22 . A vaccine comprising a fusion protein according to any one of claims  19 - 20  and a non-specific immune response enhancer.  
     
     
         23 . The vaccine of  claim 22  wherein the non-specific immune response enhancer is an adjuvant.  
     
     
         24 . A method for inhibiting the development of prostate cancer in a patient, comprising administering to the patient an effective amount of the pharmaceutical composition of  claim 21 .  
     
     
         25 . A method for inhibiting the development of prostate cancer in a patient, comprising administering to the patient an effective amount of the vaccine of  claim 22.