Prostate cancer vaccine

Abstract

Androgen receptor-based vaccines for eliciting an immune reaction in vivo against cells expressing androgen receptor are disclosed. The vaccines are useful in the treatment of prostate cancer. Also disclosed are methods for inducing immune reaction to androgen receptor or treating prostate cancer in a mammal, using the vaccines and pharmaceutical compositions comprising the vaccines.

We claim: 
     
         1 . A DNA vaccine comprising a plasmid vector comprising a polynucleotide operatively linked to a transcriptional regulatory element wherein the polynucleotide encodes a member selected from (i) a mammalian androgen receptor, (ii) a fragment of the androgen receptor that comprises a ligand-binding domain, (iii) a fragment of the ligand-binding domain defined by SEQ ID NO:9, (iv) a fragment of the ligand-binding domain defined by SEQ ID NO:10, (v) a fragment of the ligand-binding domain defined by SEQ ID NO:11, and (vi) a fragment of the ligand-binding domain defined by SEQ ID NO:12, wherein upon administration of said vaccine to a mammal a cytotoxic immune reaction against cells expressing androgen receptor is induced. 
     
     
         2 . The DNA vaccine of  claim 1 , wherein the plasmid vector comprises
 (a) a backbone of pNGVL3;   (b) a polynucleotide operably inserted therein wherein the polynucleotide encodes a member selected from (i) a mammalian androgen receptor, (ii) a fragment of the androgen receptor that comprises a ligand-binding domain, (iii) a fragment of the ligand-binding domain defined by SEQ ID NO:9, (iv) a fragment of the ligand-binding domain defined by SEQ ID NO:10, (v) a fragment of the ligand-binding domain defined by SEQ ID NO:11, and (vi) a fragment of the ligand-binding domain defined by SEQ ID NO:12; and optionally   (c) an immunostimulatory sequence (ISS) motif.   
     
     
         3 . The DNA vaccine of  claim 1 , wherein the plasmid vector comprises
 (a) a polynucleotide operatively linked to a CMV promoter wherein the polynucleotide encodes a member selected from (i) a mammalian androgen receptor, (ii) a fragment of the androgen receptor that comprises a ligand-binding domain, (iii) a fragment of the ligand-binding domain defined by SEQ ID NO:9, (iv) a fragment of the ligand-binding domain defined by SEQ ID NO:10, (v) a fragment of the ligand-binding domain defined by SEQ ID NO:11, and (vi) a fragment of the ligand-binding domain defined by SEQ ID NO:12;   (b) a CMV intron A operatively linked to the polynucleotide for enhancing expression of the polynucleotide; and optionally   (c) at least one copy of an immunostimulatory fragment comprising 5′-GTCGTT-3′.   
     
     
         4 . A pharmaceutical composition comprising the DNA vaccine of  claim 1 , and a pharmaceutically acceptable carrier. 
     
     
         5 . A pharmaceutical composition comprising the DNA vaccine of  claim 4 , further comprising an adjuvant. 
     
     
         6 . The pharmaceutical composition of  claim 5 , wherein the adjuvant is GM-CSF. 
     
     
         7 . A DNA vaccine comprising the pTVG-ARLBD plasmid vector. 
     
     
         8 . A pharmaceutical composition comprising the DNA vaccine of  claim 7  and a pharmaceutically acceptable carrier.