Chimeric antigen receptor-transduced T cells (CAR-T cells) show remarkable efficacy for some hematological malignancies. However, CAR targets are restricted to a few antigens, mostly due to the on-target off-tumor toxicity of CAR-T cells. Although several strategies have been proposed to avoid on-target off-tumor toxicity, most are complicated, including dual gene expression for specificity. In this study, we show that switchable CAR-T cells with a tumor-targeting adaptor can mitigate on-target off-tumor toxicity against a tumor antigen that cannot be targeted by conventional CAR-T cells because of this toxicity, such as CD40. Moreover, simple replacement of the tumor-targeting adaptor with a suicidal drug-conjugated tag can be used for in vivo depletion of the switchable CAR-T cells when their permanent elimination is necessary for long-term safety. Therefore, our switchable CAR system can control CAR-T cell toxicity while maintaining therapeutic efficacy, thereby expanding the targets of CAR.