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:
Jul. 30, 2024

Filed:

Jun. 05, 2017
Applicant:

University of Pittsburgh—of the Commonwealth System of Higher Education, Pittsburgh, PA (US);

Inventor:

Greg M. Delgoffe, Pittsburgh, PA (US);

Attorney:
Primary Examiner:
Int. Cl.
CPC ...
A61K 35/17 (2015.01); A61K 31/341 (2006.01); A61K 31/429 (2006.01); A61K 31/4439 (2006.01); A61K 31/498 (2006.01); A61K 31/5377 (2006.01); A61K 31/7056 (2006.01); A61K 38/17 (2006.01); A61K 38/20 (2006.01); A61K 39/00 (2006.01); A61K 39/39 (2006.01); A61K 45/06 (2006.01); A61P 35/00 (2006.01); C07K 16/28 (2006.01); C12N 5/0783 (2010.01); A61K 45/00 (2006.01);
U.S. Cl.
CPC ...
A61K 35/17 (2013.01); A61K 31/341 (2013.01); A61K 31/429 (2013.01); A61K 31/4439 (2013.01); A61K 31/498 (2013.01); A61K 31/5377 (2013.01); A61K 31/7056 (2013.01); A61K 38/1774 (2013.01); A61K 38/2013 (2013.01); A61K 39/00119 (2018.08); A61K 39/39 (2013.01); A61K 45/06 (2013.01); A61P 35/00 (2018.01); C07K 16/2809 (2013.01); C07K 16/2818 (2013.01); C07K 16/2827 (2013.01); C12N 5/0636 (2013.01); A61K 2039/5158 (2013.01); A61K 2039/876 (2018.08); A61K 45/05 (2013.01); A61K 2800/78 (2013.01); C12N 2501/39 (2013.01); C12N 2501/999 (2013.01);
Abstract

The present disclosure provides methods for expanding tumor-infiltrating lymphocytes (TILs), such as tumor-infiltrating T cells, utilizing an agonist of PGC1α in vivo, ex vivo, or both. Exhausted T cells present in the TIL population fail to effectively proliferate, produce cytokines, or kill target cells. The present disclosure provides methods to correct these defects through the use of pharmacologic agents to reprogram the metabolism of the exhausted intratumoral T cells. Exemplary agonists of PGC1α include proliferator-activated receptor (PPAR)-gamma agonists (e.g., a thiazolidinedione (TZD), aleglitazar, farglitazar, muraglitazar, or tesaglitazar), AMPK activators (e.g., 5-aminoimidazole-4-carboxamide ribonucleotide, AICAR), and sirtuin activators (e.g., resveratrol, SRT1720, SRT2104, SRT2183, SRT1460). Also provided are kits can compositions that can be used with such methods.


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