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IMMUNOTHERAPY

TKI-based on/off switch for CAR T cells

Nature Reviews Clinical Oncology volume 16, page 528 (2019)Cite this article

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Chimeric antigen receptor (CAR) T cells have promising anticancer activity but often cause serious, and potentially fatal, toxicities, most commonly cytokine-release syndrome (CRS). Now, preclinical evidence suggests that a pharmacological ‘on/off switch’ can be used to improve the safety of CAR T cell therapy.

In co-culture experiments, the tyrosine kinase inhibitor (TKI) dasatinib at a concentration that can routinely be achieved in patients (100 nM) rapidly and completely abrogated CD8+ CAR T cell activation, proliferation and cytotoxicity. These effects lasted for >12 hours and were accompanied by complete inhibition of IFNγ, IL-2 and/or GM-CSF secretion by CD8+ or CD4+ CAR T cells. By contrast, dexamethasone, which is often used to treat severe CRS, suppressed the production of IL-2 but not IFNγ.

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Original article

  • Mestermann, K. et al. The tyrosine kinase inhibitor dasatinib acts as a pharmacologic on/off switch for CAR T cells. Sci. Transl Med. 11, eaau5907 (2019)

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  1. Nature Reviews Clinical Oncology http://www.nature.com/nrclinonc

    David Killock

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  1. David Killock
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Correspondence to David Killock.

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Killock, D. TKI-based on/off switch for CAR T cells. Nat Rev Clin Oncol 16, 528 (2019). https://doi.org/10.1038/s41571-019-0258-5

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