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, comprising administering to the mammal an effective amount of a recombinant DNA construct comprising a polynucleotide operatively linked to a transcriptional regulatory element wherein the polynucleotide encodes a member selected from a group consisting of (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, whereby the mammal develops immune reaction against androgen receptor.
2. The method of claim 1 , wherein the polynucleotide encodes the ligand-binding domain of the androgen receptor.
3. The method of claim 2 , wherein the androgen receptor is a human androgen receptor.
4. The method of claim 3 , wherein the polynucleotide encodes a fragment of SEQ ID NO:2 wherein the fragment starts from a position ranging from amino acid 651 to amino acid 681 of SEQ ID NO:2 and ends at a position ranging from amino acid 900 to amino acid 920 of SEQ ID NO:2.
5. The method of claim 1 , wherein the recombinant DNA construct is administered to the mammal intradermally, intramuscularly, intravascularly, or subcutaneously.
6. The method of claim 1 , wherein the mammal is a human.
7. The method of claim 1 , wherein cellular immune reaction against cells expressing androgen receptor is induced.
8. The method of claim 7 , wherein both humoral and cellular immune reactions against androgen receptor are induced.
9. A method for inducing an immune reaction to androgen receptor in a mammal having prostate cancer, comprising administering to the mammal an effective amount of a recombinant DNA construct comprising a polynucleotide encoding amino acids 664-920 of SEQ ID NO:2 operatively linked to a transcriptional regulatory element whereby the mammal develops immune reaction against androgen receptor.
10. The method of claim 9 , wherein the mammal is a human being.