Prostate cancer vaccine
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.
1. A DNA vaccine comprising a plasmid vector comprising (a) a polynucleotide operatively linked to a transcriptional regulatory element, the polynucleotide encoding a polypeptide that consists of one of SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, and SEQ ID NO:12, and (b) at least one immunostimulatory sequence (ISS) motif (5′-GTCGTT-3′), 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 polypeptide that consists of one of SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, and SEQ ID NO:12; and
(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 polypeptide that consists of one of SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, and SEQ ID NO:12;
(b) a CMV intron A operatively linked to the polynucleotide for enhancing expression of the polynucleotide; and
(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.