Organizer: IRB Barcelona
Date: Tuesday 11 May 2021, 15:00h
Title: From Cancer to Aging: Harnessing CAR T cells to Deconstruct Senescence
Host: Manuel Serrano, PhD
Cellular senescence is a stress-response program that is characterized by stable cell cycle arrest and increased secretion of factors that modulate the tissue microenvironment. Physiologically, the senescence program serves as a potent tumor suppresive mechanism that prevents the expansion of premalignant cells and plays a beneficial role in certain wound healing responses. However, the pathological accumulation of senescent cells generates a chronic inflammatory milieu that contributes to tissue decline and a plethora of pathologies, including liver and lung fibrosis, severe atherosclerosis, diabetes and osteoarthritis. Experimental strategies to eliminate senescent cells from damaged tissues can ameliorate these pathologies in mice, and even promote longevity. Here we test the therapeutic concept that chimeric antigen receptor (CAR) T cells targeting senescent cells could serve as effective senolytics. Remarkably, treatment of senescence-associated liver fibrosis with senolytic CAR T cells leads to resolution of fibrosis and enhanced liver function in both non-alcoholic steatohepatitis (NASH) and in chemical induced fibrosis. Furthermore, senolytic CAR T cells are also therapeutic in a model on non-small cell lung cancer through a one-two punch senogenic-senolytic approach. These results establish the potential for using CAR T cells as senolytic agents for study and treatment of a broad range of senescence-associated diseases.
Open to predoctoral UPF students
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