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 method for inducing an immune reaction to androgen receptor in a mammal having prostate cancer, the method comprising the step of:
administering to the mammal an effective amount of a DNA vaccine comprising a polynucleotide operatively linked to a transcriptional regulatory element,
wherein the polynucleotide encodes a fragment of a mammalian androgen receptor consisting essentially of the ligand-binding domain of the receptor, the ligand-binding domain fragment selected from the group consisting of (i) SEQ ID NO:9, (ii) SEQ ID NO:10, (iii) SEQ ID NO:11, and (iv) SEQ ID NO:12,
whereby the mammal develops an immune reaction against androgen receptor.
2. The method of claim 1 , wherein said DNA vaccine is administered in a pharmaceutically acceptable carrier.
3. The method of claim 1 , wherein the DNA vaccine is a plasmid vector that comprises:
(a) a backbone of pNGVL3;
(b) the polynucleotide operably positioned in the backbone; and optionally
(c) an immunostimulatory sequence (ISS) motif.
4. The method of claim 3 , wherein:
(a) the polynucleotide is operatively linked to a CMV promoter and to a CMV intron A for enhancing expression of the polynucleotide; and optionally
(b) the optional immunostimulatory sequence (ISS) motif comprises at least one copy of 5′-GTCGTT-3′.
5. The method of claim 1 , wherein the fragment is a fragment of a human androgen receptor.
6. The method of claim 1 , wherein the vaccine is administered with a suitable amount of GM-CSF.
7. A method for inducing an immune reaction to androgen receptor in a mammal having prostate cancer, the method comprising the step of:
administering to the mammal an effective amount of a plasmid vector comprising a polynucleotide operatively linked to a transcriptional regulatory element wherein the polynucleotide encodes a fragment of a mammalian androgen receptor consisting essentially of the ligand-binding domain of the receptor, the ligand-binding domain fragment selected from the group consisting of (i) SEQ ID NO:9, (ii) SEQ ID NO:10, (iii) SEQ ID NO:11, and (iv) SEQ ID NO:12,
whereby the mammal develops immune reaction against androgen receptor.
8. The method of claim 7 , wherein the plasmid vector comprises:
(a) a backbone of pNGVL3;
(b) the polynucleotide operably positioned in the backbone; and optionally
(c) an immunostimulatory sequence (ISS) motif.
9. The method of claim 7 , wherein the plasmid vector comprises
(a) the polynucleotide operatively linked to a CMV promoter and to a CMV intron A for enhancing expression of the polynucleotide; and optionally
(b) the optional immunostimulatory sequence (ISS) motif comprises at least one copy of 5′-GTCGTT-3′.
10. The method of claim 7 , wherein the fragment of a mammalian androgen receptor is a fragment of a human androgen receptor.
11. The method of claim 7 , wherein the plasmid vector is administered in a pharmaceutically acceptable carrier.
12. The method of claim 7 , wherein the plasmid vector is administered with a suitable amount of GM-CSF.