The patent badge is an abbreviated version of the USPTO patent document. The patent badge does contain a link to the full patent document.

The patent badge is an abbreviated version of the USPTO patent document. The patent badge covers the following: Patent number, Date patent was issued, Date patent was filed, Title of the patent, Applicant, Inventor, Assignee, Attorney firm, Primary examiner, Assistant examiner, CPCs, and Abstract. The patent badge does contain a link to the full patent document (in Adobe Acrobat format, aka pdf). To download or print any patent click here.

Date of Patent:
Mar. 04, 2025

Filed:

Oct. 07, 2016
Applicants:

The Brigham and Women's Hospital, Inc., Boston, MA (US);

The Broad Institute, Inc., Cambridge, MA (US);

Massachusetts Institute of Technology, Cambridge, MA (US);

Inventors:

Vijay K. Kuchroo, Boston, MA (US);

Ana C. Anderson, Boston, MA (US);

Asaf Madi, Boston, MA (US);

Norio Chihara, Boston, MA (US);

Aviv Regev, Cambridge, MA (US);

Meromit Singer, Cambridge, MA (US);

Assignees:
Attorney:
Primary Examiner:
Int. Cl.
CPC ...
A61K 35/17 (2015.01); A61K 39/00 (2006.01); A61K 39/39 (2006.01); A61P 31/04 (2006.01); A61P 31/12 (2006.01); A61P 35/00 (2006.01); C07K 14/705 (2006.01); C12N 5/0783 (2010.01); C12N 15/62 (2006.01); C12Q 1/6827 (2018.01); C12Q 1/686 (2018.01); C12Q 1/6881 (2018.01);
U.S. Cl.
CPC ...
C07K 14/705 (2013.01); A61K 39/39 (2013.01); A61K 39/4611 (2023.05); A61K 39/464492 (2023.05); A61P 31/04 (2018.01); A61P 31/12 (2018.01); A61P 35/00 (2018.01); C12N 5/0636 (2013.01); C12N 15/62 (2013.01); C12Q 1/6827 (2013.01); C12Q 1/686 (2013.01); C12Q 1/6881 (2013.01); A61K 2239/31 (2023.05); A61K 2239/57 (2023.05); C12N 2501/2327 (2013.01); C12N 2510/00 (2013.01);
Abstract

Dysfunctional or exhausted T cells arise in chronic diseases including chronic viral infections and cancer, and express high levels of co-inhibitory receptors. Therapeutic blockade of these receptors has clinical efficacy in the treatment of cancer. While co-inhibitory receptors are co-expressed, the triggers that induce them and the transcriptional regulators that drive their co-expression have not been identified. The immunoregulatory cytokine IL-27 induces a gene module in T cells that includes several known co-inhibitory receptors (Tim-3, Lag-3, and TIGIT). The present invention provides a novel immunoregulatory network as well as novel cell surface molecules that have an inhibitory function in the tumor microenvironment. The present invention further provides the novel discovery that the transcription factors Prdm1 and c-Maf cooperatively regulate the expression of the co-inhibitory receptor module. This critical molecular circuit underlies the co-expression of co-inhibitory receptors in dysfunctional T cells and identifies novel regulators of T cell dysfunction.


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