Yan Leyfman: Boosting CAR-T/NK Cell Persistence via the FAS Pathway
Yan Leyfman, Medical Correspondent of OncLive, shared a post on LinkedIn about an article by Fei Yi et al.:
“Boosting CAR-T/NK Cell Persistence via the FAS Pathway
Chimeric antigen receptor (CAR) T and NK cell therapies have transformed treatment for B-cell malignancies – but limited cell persistence remains a key barrier.
In a new study led by Dr. Christopher A. Klebanoff, M.D. (Memorial Sloan Kettering Cancer Center), researchers mapped FAS ligand (FAS-L) expression across cancer types at the single-cell level and found that CAR-T, T, and NK cells themselves are the main sources of FAS-L—not tumor or stromal cells.
– They engineered CAR cells with a dominant-negative FAS receptor (ΔFAS) to block this self-regulatory death signal.
– Result? FAS-CAR-T/NK cells persisted longer and showed enhanced antitumor activity—without compromising tumor killing.
– Knocking out FASLG reversed the fitness benefit, proving the effect is mediated by this axis.
– Key insight: CAR cell persistence is regulated by a FAS-L/FAS auto-regulatory loop. Disrupting this loop may be a powerful way to amplify CAR-based therapies.”
Title: CAR-engineered lymphocyte persistence is governed by a FAS ligand/FAS auto-regulatory circuit
Authors: Fei Yi, Tal Cohen, Natalie Zimmerman, Friederike Dündar, Paul Zumbo, Razan Eltilib, Erica J Brophy, Hannah Arkin, Judith Feucht, Michael V Gormally, Christopher S Hackett, Korbinian N Kropp, Inaki Etxeberria, Smita S Chandran, Jae H Park, Katharine C Hsu, Michel Sadelain, Doron Betel, Christopher A Klebanoff
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