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The study aims to assess the impact of reversible and irreversible BTK inhibitors on the properties of CAR T cells in treating mantle cell lymphoma.

July 11, 2026LeukemiaOpen Access

Reversible and irreversible BTK inhibition promotes stem-like functional multipotency, persistence, and antitumor efficacy of CD19-directed CAR T cells in mantle cell lymphoma

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The study aims to assess the impact of reversible and irreversible BTK inhibitors on the properties of CAR T cells in treating mantle cell lymphoma.
Re-analyzed single-cell RNA-seq data from MCL patients pre- and post-PBN treatment.
Generated CD19-directed CAR T cells incorporating BTK inhibitors during T-cell activation and transduction.
Evaluated CAR T cells' effector responses and metabolic function through various assays.
PBN treatment increased naïve-like and early activated CD8+ T cells and upregulated stemness markers like IL7R and CD62L post-treatment.
KI-modulated CAR T cells showed enhanced T-cell persistence, metabolic fitness, and significantly improved tumoricidal activity in MCL cell models.
In vivo, PBN enhanced tumor control and prolonged survival in mouse models of MCL following CD19-CAR T therapy.

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Randomized trial evaluates BTK inhibitor effects on CAR T-cell function in mantle cell lymphoma, suggesting improved outcomes.

Yao et al. (2026) studied this question.

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