Compounds for inducing anti-tumor immunity and methods thereof
Described herein is a previously unknown function of XBP1 in controlling anti-tumor immunity. It is shown that inhibiting XBP1 in tumor-associated dendritic cells inhibits tumor growth and induces protective anti-tumor immune responses.
1. A method for treatment of cancer in a subject in need thereof, the method comprising:
contacting antigen presenting cells (APCs) with a direct inhibitor of IRE-1α, wherein the direct inhibitor of IRE1α is present in an amount sufficient to increase antigen presentation in the APCs; and
administering the APCs contacted with the direct inhibitor of IRE-1α, to a subject, wherein the subject has a solid cancer, and wherein the solid cancer comprises an epithelial cancer, a germ cell cancer, or a stromal tumor.
2. The method of claim 1 , wherein the solid cancer is further characterized as an ovarian cancer.
3. The method of claim 1 , wherein the epithelial cancer is a carcinoma or an adenocarcinoma.
4. The method of claim 1 , wherein the APCs are dendritic cells.
5. The method of claim 4 , wherein the dendritic cells are tumor-associated dendritic cells.
6. The method of claim 1 , wherein the APCs provided are obtained from the subject.
7. The method of claim 1 , wherein the direct inhibitor of IRE-1α is an IRE-1α-specific antibody or a small molecule inhibitor of IRE-1α.
8. The method of claim 1 , wherein the direct inhibitor of IRE-1α reduces or eliminates IRE-1α mRNA expression in the APCs.
9. The method of claim 1 , wherein the direct inhibitor of IRE-1α reduces or eliminates IRE-1α protein expression in the APCs.
10. The method of claim 1 , wherein the direct inhibitor of IRE-1α is a nucleic acid molecule that is antisense to an IRE-1α-encoding nucleic acid molecule, an IRE-1α shRNA, an IRE-1α siRNA, or a microRNA that targets IRE-1α.
11. The method of claim 1 , further comprising administering an additional therapeutic agent to the subject.
12. The method of claim 11 , wherein the additional therapeutic agent is a chemotherapeutic agent or an antibody.
13. A method for treatment of ovarian cancer in a subject in need thereof, the method comprising:
contacting antigen presenting cells (APCs) with a small molecule inhibitor of IRE-1α, wherein the small molecule inhibitor of IRE1α is present in an amount sufficient to increase antigen presentation in the APCs; and
administering the APCs contacted with the small molecule inhibitor of IRE-1α to a subject, wherein the subject has ovarian cancer.
14. The method of claim 13 , wherein the APCs are dendritic cells.
15. The method of claim 13 , wherein the APCs provided are obtained from the subject.
16. A method for treatment of ovarian cancer in a subject in need thereof, the method comprising:
contacting antigen presenting cells (APCs) with an inhibitor of IRE-1α, wherein the inhibitor of IRE1α is present in an amount sufficient to increase antigen presentation in the APCs, and wherein the inhibitor of IRE-1α reduces or eliminates IRE-1α mRNA expression in the APCs; and
administering the APCs contacted with the inhibitor of IRE-1α to a subject, wherein the subject has ovarian cancer.
17. The method of claim 16 , wherein the APCs are dendritic cells.
18. The method of claim 16 , wherein the APCs provided are obtained from the subject.
19. The method of claim 16 , wherein the inhibitor of IRE-1α is a nucleic acid molecule that is antisense to an IRE-1α-encoding nucleic acid molecule, an IRE-1α shRNA, or an IRE-1α siRNA.