Michael Green, Professor and Vice Chair for Research in the Department of Lymphoma and Myeloma at MD Anderson Cancer Center, shared on LinkedIn:
“I’m pleased to share our most recent manuscript, published online in Blood.
Using scRNA-seq of post-CAR T biopsies, we found that CAR T cells can remain detectable at the time of progression in some patients, with active CAR+ CD8 T-cell proliferation and trajectories toward terminal exhaustion.
We modeled this in vitro using patient-derived CAR T cells and showed that serial tumor-cell engagement drives exhaustion, in part through loss of IL-2 signaling.
This exhaustion could be mitigated using a non-alpha IL-2 agonist, offering a potential strategy to support CAR T-cell function in patients with high tumor burden, particularly those who do not respond well to bridging therapy.
The paper also describes a PDX-derived cell-line model from a CAR T relapse tumor, providing a disease-relevant system for testing future interventions.
Title: CD8 T-cell exhaustion linked with CAR T-cell failure can be mitigated by a non-alpha IL2 receptor agonist
Authors: Kotaro Arita, Enyu Dai, Xubin Li, Irtiza N. Sheikh, Patrick K Reville, Jared Henderson, Ashley Lauren Wilson, Christan Dillard, Kevin Bowman, Haopeng Yang, Fuliang Chu, Robert Andrew Harkins, Nathan Michael Pate, Katie Malley, Dinesh S Bangari, Estela Rojas, Jason R Westin, Sairah Ahmed, Sattva S. Neelapu, Francisco Vega, Rui Wang, Xiangming Li, Donald Shaffer, Linghua Wang, Michael R GreenCorresponding
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