Combinatorial androgen deprivation with an androgen receptor vaccine
AssigneeWisconsin Alumni Research Foundation
InventorsDouglas McNeel, Brian Olson
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Abstract
It is disclosed herein methods of treating prostate cancer comprising administering to the subject the combination of androgen deprivation therapy (ADT) and a vaccine directed against the androgen receptor or a fragment of the androgen receptor. Also disclosed are methods of increasing the efficacy of androgen deprivation therapy in a subject with prostate cancer comprising administering to the subject an effective amount of a vaccine against the androgen receptor or fragments thereof wherein the method inhibits, delays or reduces the growth of the prostate cancer and/or the development of castration-resistant prostate cancer.
Claims19
A method of eliciting an anti-tumor response in a subject having prostate cancer comprising:
- a. administering to the subject androgen deprivation therapy (ADT) comprising degarelix;
- and
- b. administering to the subject a recombinant DNA vaccine comprising a polynucleotide operably linked to a transcriptional regulatory element wherein the polynucleotide encodes an androgen receptor or a fragment of the androgen receptor selected from the 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 DNA vaccine elicits an immune response in the subject against the androgen receptor,
- wherein the recombinant DNA vaccine is administered in an amount effective to elicit an increased anti-tumor response to the prostate cancer, wherein the combination treatment of ADT and the recombinant DNA vaccine inhibits, delays or reduces the growth of the prostate cancer.
A method of eliciting an anti-tumor response in a subject having prostate cancer comprising:
- a. administering to the subject androgen deprivation therapy (ADT) comprising degarelix;
- b. administering to the subject a recombinant DNA vaccine comprising a polynucleotide operably linked to a transcriptional regulatory element wherein the polynucleotide encodes an androgen receptor or a fragment of the androgen receptor selected from the 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 DNA vaccine elicits an immune response in the subject against the androgen receptor, and
- c. administering to the subject an effective amount of a PD-pathway inhibitor,
- wherein the recombinant DNA vaccine and PD-pathway inhibitor are administered in an amount effective to elicit an increased anti-tumor response to the prostate cancer, wherein the combination treatment of ADT, the recombinant DNA vaccine and PD-pathway inhibitor inhibits, delays or reduces the growth of the prostate cancer.
Dependencies are inferred from the claim text.