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 enhancing or inducing an anti-tumor response in a subject, the method comprising:
administering to the subject an effective amount of a direct inhibitor of IRE1α for enhancing or inducing an anti-tumor immune response in the subject, wherein the effective amount of the direct inhibitor of IRE1α increases antigen presentation in antigen presenting cells, wherein the tumor is a solid tumor, wherein the solid tumor is from an ovarian cancer, epithelial cancer, germ cell cancer, or a stromal tumor, and wherein the direct inhibitor of IRE1α is a small molecule inhibitor of IRE-1α.
2. The method of claim 1 , wherein the inhibitor of IRE-1α is administered systemically.
3. The method of claim 1 , wherein the inhibitor of IRE-1α, targets tumor-associated dendritic cells (tDCs).
4. The method of claim 1 , wherein the inhibitor of IRE-1α is administered in combination with a second cancer therapeutic agent.
5. The method of claim 4 , wherein the second cancer therapeutic agent is a chemotherapeutic agent.
6. The method of claim 1 , wherein the treatment induces extended survival of the subject.
7. The method of claim 1 , wherein the anti-tumor immune response is mediated by adaptive immune cells.
8. The method of claim 7 , wherein the adaptive immune cells comprise T cells.
9. The method of claim 1 wherein the solid tumor is from an ovarian cancer.
10. The method of claim 1 wherein the solid tumor is from an epithelial cancer.
11. The method of claim 1 wherein the solid tumor is from a germ cell cancer.
12. The method of claim 1 wherein the solid tumor is a stromal tumor.