Compounds for inducing anti-tumor immunity and methods thereof

• US 9,957,506 B2
• Filed: 09/25/2014
• Issued: 05/01/2018
• Est. Priority Date: 09/25/2013
• Status: Active Grant

• Current Assignee: Cornell University
• Original Assignee: Cornell University
• Inventors: Cubillos-Ruiz, Juan R., Glimcher, Laurie H.
• Primary Examiner(s): Chong, Kimberly
• Application Number:
  US15/024,215
• Publication Number:
  US 20160237429A1
• Time in Patent Office: 1,314 Days
• CPC Class Codes: A61K 31/713 Double-stranded nucleic acids or oligonucleotides
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: C12N 15/113 Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing when used in plants C12N15/8218
• CPC Class Codes: C12N 15/1137 against enzymes viral enzymes C12N15/1131; receptors C12N15/1138
• CPC Class Codes: C12N 2310/11 Antisense
• CPC Class Codes: C12N 2310/14 interfering N.A.
• CPC Class Codes: C12N 2320/31 Combination therapy
• CPC Class Codes: C12Y 207/11 Protein-serine/threonine kinases (2.7.11)

Abstract

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.

Claims

1. A method for enhancing or inducing an anti-tumor immune response in a subject, 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 IRE1α

increases antigen presentation in antigen presenting cells, wherein the tumor is a solid tumor, and wherein the solid tumor is from an ovarian cancer, epithelial cancer, germ cell cancer, a stromal tumor.

2. The method of claim 1, wherein the epithelial cancer is a carcinoma or an adenocarcinoma.

3. 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

.

4. The method of claim 1, wherein the direct inhibitor of IRE-1α

is administered systemically or at tumor locations in the subject.

5. The method of claim 1, wherein the direct inhibitor of IRE-1α

targets tumor-associated dendritic cells (tDCs).

6. The method of claim 1, wherein the direct inhibitor of IRE-1α

is administered in combination with a second cancer therapeutic agent.

7. The method of claim 6, wherein the second cancer therapeutic agent is a chemotherapeutic agent.

8. The method of claim 1, wherein the treatment induces extended survival of the subject.

9. The method of claim 1, wherein the anti-tumor immune response is mediated by adaptive immune cells.

10. The method of claim 9, wherein the adaptive immune cells comprise T cells.