USE OF PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR GAMMA COACTIVATOR 1-ALPHA (PGC1ALPHA) AGONISTS TO IMPROVE EX VIVO EXPANSION OF TUMOR INFILTRATING LYMPHOCYTES (TILS)
University of Pittsburgh - Of the Commonwealth System of Higher Education
发明人:
Greg M. Delgoffe
申请号：
US16303828
公开号：
US20190307796A1
申请日:
2017.06.05
申请国别(地区):
US
年份:
2019
代理人:
摘要：
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.
