Compounds for inducing anti-tumor immunity and methods thereof

Patent metadata

Field	Value
Publication number	US-2016237429-A1
Application number	US-201415024215-A
Country	US
Kind code	A1
Filing date	Sep 25, 2014
Priority date	Sep 25, 2013
Publication date	Aug 18, 2016
Grant date	—

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.

First claim

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 or indirect inhibitor of XBP1, thereby enhancing or inducing the anti-tumor immune response in the subject.

2 . A method for treating or reducing the progression of ovarian cancer in a subject, comprising administering to the subject an effective amount of a direct or indirect inhibitor of XBP1, thereby treating or reducing the progression of ovarian cancer in the subject.

3 . A method for enhancing or inducing the immune response of cancer-associated dendritic cells in a subject comprising administering to the subject an effective amount of a direct or indirect inhibitor of XBP1, thereby enhancing or inducing the immune response of cancer-associated dendritic cells in the subject.

4 . The method of claim 1 , wherein the subject has ovarian cancer.

5 . The method of claim 1 , wherein the inhibitor of XBP1 is a direct inhibitor.

6 . The method of claim 1 , wherein the inhibitor of XBP1 is selected from the group consisting of a nucleic acid molecule that is antisense to an XBP1-encoding nucleic acid molecule, an XBP1 shRNA, and XBP1 siRNA, a microRNA that targets XBP1, a nanoparticle-encapsulated XBP1 siRNA, a dominant negative XBP1 molecule, an XBP1-specific antibody and a small molecule inhibitor of XBP1.

7 . The method of claim 1 , wherein the inhibitor of XBP1 is an XBP1 shRNA or an XBP1 siRNA.

8 . The method of claim 1 , wherein the inhibitor of XBP1 is a nanoparticle-encapsulated XBP1-specific siRNA.

9 . The method of claim 1 , wherein the inhibitor of XBP1 is an indirect inhibitor.

10 . The method of claim 9 , wherein the inhibitor of XBP1 is an agent that inhibits IRE-1α or an agent that inhibits the generation of functional XBP1.

11 . The method of claim 10 , wherein the inhibitor of IRE-1α is an IRE-1α shRNA or an IRE-1αsiRNA.

12 . The method of claim 10 , wherein the agent that inhibits IRE1α is a nanoparticle-encapsulated IRE-1α specific siRNA.

13 . The method of claim 1 , wherein the inhibitor of XBP1 is administered systemically or at tumor locations in the subject.

14 . The method of claim 13 , wherein the tumor is an ovarian cancer.

15 . The method of claim 1 , wherein the inhibitor of XBP1 targets tumor-associated dendritic cells (tDCs)

16 . The method of claim 1 , wherein the inhibitor of XBP1 is administered in combination with a second cancer therapeutic agent.

17 . The method of claim 16 , wherein the inhibitor of XBP1 is administered in combination with a chemotherapeutic agent.

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

19 . 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 or indirect inhibitor of IRE1α, thereby enhancing or inducing the anti-tumor response in the subject.

20 . The method of claim 19 , wherein the subject has ovarian cancer.

21 . The method of claim 19 , wherein the inhibitor of IRE-1α is a direct inhibitor.

22 . The method of claim 19 , wherein the inhibitor of IRE-1α is selected from the group consisting of a nucleic acid molecule that is antisense to an IRE-1α encoding nucleic acid molecule, an IRE-1αshRNA, and IRE-1αsiRNA, a microRNA that targets IRE1α, a nanoparticle-encapsulated IRE-1α siRNA, a dominant negative IRE-1α molecule, an IRE-1α-specific antibody and a small molecule inhibitor of IRE-1α.

23 . The method of claim 22 , wherein the inhibitor of IRE-1α is an IRE-1αshRNA or an IRE-1αsiRNA.

24 . The method of claim 22 , wherein the inhibitor of IRE-1α is a nanoparticle-encapsulated IRE-1α-specific siRNA.

25 . The method of claim 19 , wherein the inhibitor of IRE-1α is an indirect inhibitor.

26 . The method of claim 19 , wherein the inhibitor of IRE-1α is administered systemically or at tumor locations in the subject.

27 . The method of claim 26 , wherein the tumor is an ovarian cancer.

28 . The method of claim 19 , wherein the inhibitor of IRE-1α targets tumor-associated dendritic cells (tDCs)

29 . The method of claim 19 , wherein the inhibitor of IRE-1α is administered in combination with a second cancer therapeutic agent.

30 . The method of claim 29 , wherein the inhibitor of IRE-1α is administered in combination with a chemotherapeutic agent.

31 . The method of claim 19 , wherein the treatment induces extended survival of the subject.

Assignees

• Univ Cornell

Inventors

• Cubillos-Ruiz Juan R
• Glimcher Laurie H

Classifications

• C12N2310/14

  interfering nucleic acids [NA] · CPC title

• C12N2320/31

  Combination therapy · CPC title

• A61K31/713

  Double-stranded nucleic acids or oligonucleotides · CPC title

• C12Y207/11

  Protein-serine/threonine kinases (2.7.11) · CPC title

• C12N15/113 Primary

  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 title