Yan Leyfman, Executive Committee Member at Music Beats Cancer, shared on LinkedIn:
“How long can CAR-T cells actually last?
We often talk about CAR-T as a one-time treatment.
But what if the cells themselves remain active in the body for a decade?
A remarkable new study followed 4-1BB-costimulated CD19 CAR-T cells for up to 10 years in patients with non-Hodgkin lymphoma-and provides some of the clearest evidence yet of exceptionally long-term CAR-T persistence.
38 patients were followed long term
CAR19 cells remained detectable 7–10 years after infusion in 5 of 8 long-term responders
3 patients-maintained B-cell aplasia, suggesting continued functional activity
In one patient with 10.1 years of progression-free survival, CAR-T cells still represented 1.2% of circulating T cells nearly a decade after treatment
Persisting cells progressively shifted from CD8⁺ toward CD4⁻CD8⁻ double-negative, effector-memory-like CAR-T cells
These long-lived cells demonstrated enhanced metabolic and T-cell activation programs
TCR sequencing revealed oligoclonal persistence, with a dominant clone detectable as early as day 14
Perhaps most fascinating: the dominant CAR-T clone nearly a decade later was already present at <0.1% on day 14.
This suggests that long-term CAR-T persistence may be determined remarkably early after infusion.
The findings also challenge our traditional understanding of what a successful CAR-T cell looks like. The cells that persist for years may not simply be conventional CD8⁺ effector cells-they can evolve into a distinct, metabolically active, double-negative population capable of maintaining immune surveillance.
A single infusion. A decade later, the cells are still there.
That is one of the most remarkable features of cellular therapy-and an important clue toward designing the next generation of CAR-T products for even more durable disease control.”
Read The Full Article.
Title: Decade-long persistence of CD19 CAR T cells in B cell lymphomas
Authors: Luca Paruzzo, Emeline R. Chong, Elise A. Chong, Zhixuan Zheng, Puneeth Guruprasad, Daniel J. Landsburg, Sunita D. Nasta, Federico Stella, Ranjani Ramasubramanian, Vitor B. de Souza, Mohannad H. Alkhatib, Matthew Ho, Antonio Imparato, Gregory M. Chen, Don L. Siegel, Gabriela Plesa, Anlan Dai, Shane Mackey, Priyamvada Das, Peter Michener, Julie Jadlowsky, Frederic D. Bushman, Vrutti Patel, Alberto Carturan, Ellen B. Napier, Vanessa E. Gonzalez, Danuta Jarocha, Rong Xu, Bruce L. Levine, Patrizia Porazzi, Noelle Frey, David L. Porter, Jakub Svoboda, Joseph A. Fraietta, Carl H. June, Stephen J. Schuster and Marco Ruella
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