Methods for increasing immune responses using agents that directly bind to and activate IRE-1

• US 9,956,236 B2
• Filed: 02/07/2012
• Issued: 05/01/2018
• Est. Priority Date: 02/07/2011
• Status: Active Grant

• Current Assignee: Cornell University
• Original Assignee: Cornell University
• Inventors: Glimcher, Laurie H., Bettigole, Sarah, Martinon, Fabio
• Primary Examiner(s): Andres, Janet L
• Assistant Examiner(s): SNYDER, STUART
• Application Number:
  US13/983,180
• Publication Number:
  US 20140030294A1
• Time in Patent Office: 2,275 Days
• Field of Search: None
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/427 not condensed and containing further heterocyclic rings
• CPC Class Codes: A61K 31/44 Non condensed pyridines; Hydrogenated derivatives thereof
• CPC Class Codes: A61K 31/472 Non-condensed isoquinolines, e.g. papaverine
• CPC Class Codes: A61K 31/513 having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
• CPC Class Codes: A61K 31/675 having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 35/00 Antineoplastic agents

Abstract

The invention provides, e.g., compositions and methods for increasing activation of immune cells.

Claims

1. A method for increasing activation of immune cells in a subject, comprising administering at least one toll-like receptor (TLR) agonist and a human immunodeficiency virus (HIV) protease inhibitor that activates IRE-1 in the subject thereby increasing activation of immune cells in the subject, wherein the toll-like receptor (TLR) agonist stimulates TLR4;

and contacting the immune cells with an antigen to which an immune response is desired.

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

3. The method of claim 1, wherein production of a proinflammatory cytokine by the immune cells is increased.

4. The method of claim 3, wherein the proinflammatory cytokine is interleukin-6 (IL-6).

5. The method of claim 1, wherein the expression of at least one costimulatory molecule is increased.

6. The method of claim 5, wherein the expression of cluster of differentiation 40 (CD40) is increased.

7. The method of claim 1, wherein the immune cells comprise macrophages.

8. The method of claim 1, wherein the HIV protease inhibitor is selected from the group consisting of:

Atazanavir, Lopinavir, Nelfinavir and Ritonavir.

9. The method of claim 8, wherein the HIV protease inhibitor is Nelfinavir.

10. The method of claim 1, wherein the activation of immune cells is increased in vivo.