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 polynucleotide operatively linked to a transcriptional regulatory element wherein the polynucleotide encodes a member selected from (i) fragment of a mammalian androgen receptor consisting essentially of the ligand-binding domain defined by SEQ ID NO:9, (ii) a fragment of a mammalian androgen receptor consisting essentially of the ligand-binding domain defined by SEQ ID NO:10, (iii) a fragment of a mammalian androgen receptor consisting essentially of the ligand-binding domain defined by SEQ ID NO:11, and (iv) a fragment of a mammalian androgen receptor consisting essentially 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 fragment of a mammalian androgen receptor consisting essentially of the ligand-binding domain defined by SEQ ID NO:9, (ii) a fragment of a mammalian androgen receptor consisting essentially of the ligand-binding domain defined by SEQ ID NO:10, (iii) a fragment of a mammalian androgen receptor consisting essentially of the ligand-binding domain defined by SEQ ID NO:11, and (iv) a fragment of a mammalian androgen receptor consisting essentially 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 fragment of a mammalian androgen receptor consisting essentially of the ligand-binding domain defined by SEQ ID NO:9, (ii) a fragment of a mammalian androgen receptor consisting essentially of the ligand-binding domain defined by SEQ ID NO:10, (iii) a fragment of a mammalian androgen receptor consisting essentially of the ligand-binding domain defined by SEQ ID NO:11, and (iv) a fragment of a mammalian androgen receptor consisting essentially 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 1 , further comprising a suitable amount of GM-CSF.
6. The DNA vaccine of claim 1 , wherein the fragment of a mammalian androgen receptor is a fragment of a human androgen receptor.
7. A DNA vaccine comprising a plasmid vector comprising a polynucleotide operatively linked to a transcriptional regulatory element wherein the polynucleotide encodes a fragment of a human androgen receptor ligand binding domain consisting essentially of a fragment of SEQ ID NO:2 starting from a position ranging from amino acid 761 to amino acid 770 of SEQ ID NO:2 and ending at a position ranging from amino acid 859 to amino acid 867 of SEQ ID NO:2.