Safety control of switchable chimeric antigen receptor t cells using dose-adjustable adaptors

Abstract

Chimeric antigen receptor-transduced T cells (CAR-T cells) show a remarkable efficacy for some hematological malignancies. However, CAR targets are restricted to a few antigens primarily due to on-target off-tumor toxicities of CAR-T cells. Although several strategies were proposed to avoid on-target off-tumor toxicities, most of them use complicated designs including dual gene expression for specificity. In this study, we show that switchable CAR immune cells (e.g., CAR-T cells) with a tumor-targeting adaptor can mitigate on-target off-tumor toxicity against the tumor antigen that cannot be targeted with conventional CAR immune cells due to this toxicity, such as CD40 and CS1. Therefore, a switchable CAR system is a valuable tool to control CAR-T cell toxicity while maintaining therapeutic efficacy, which enables CAR anti-tumor target expansion.

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