A Pharmacologic Off-Switch for Split CARs
Study describes a venetoclax-regulated off-switch CAR system with dose-dependent control of receptor assembly in vitro and in vivo
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The study developed a drug-regulated off-switch protein–protein interaction CAR (DROP-CAR) using human protein components.
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Venetoclax effectively disrupts the DROP-CAR configuration, leading to near-total receptor disassembly in Jurkat cells.
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DROP-CAR T cells showed reduced interferon-γ production and cytotoxicity when treated with venetoclax, unlike second-generation CAR T cells.
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Live-cell imaging revealed that venetoclax treatment impaired immune synapse formation and altered calcium flux in DROP-CAR T cells.
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The DROP-CAR system offers a clinically feasible method to modulate CAR-T cell activity using an existing cancer therapy.
