[摘 要] 嵌合抗原受体基因修饰T淋巴细胞（CAR-T细胞）在血液系统恶性肿瘤的治疗中已取得了重大进展，但其体内行为的 不确定性和不可控性仍然限制了其临床应用。CAR-T细胞在不恰当的地点以不可控制的强度被活化，可能导致抗肿瘤作用的下 降或造成难以预测的不良反应。若能使CAR-T细胞的体内行为变得可知和可控，并在适当的地点以适宜的强度被活化，将有望 显著提升抗肿瘤疗效并降低不良反应。本文系统总结了近年来“遥控”CAR-T细胞体内活性的策略。通过巧妙的设计对CAR-T 细胞的活性和行为进行精细控制，发挥安全、精准、高效的抗肿瘤疗效是CAR-T细胞治疗未来的发展方向之一。

[Abstract] Chimeric antigen receptor gene-modified T lymphocytes (CAR-T cells) have made significant progress in the treatment of hematologic malignancies. However, the uncertainties and lack of controllability associated with their in vivo behavior remain major limitations to their clinical application. Uncontrolled or inappropriate activation of CAR-T cells at unintended locations can lead to reduced antitumor efficacy or unpredictable adverse reactions. Enabling CAR-T cells to exhibit predictable and controllable behavior in vivo, with activation occurring at the right location and at the appropriate intensity, holds the potential to significantly enhance their antitumor effectiveness and minimize adverse effects. This article systematically reviews recent strategies for "remotely controlling" CAR-T cell activity in vivo through innovative designs that allow precise regulation of CAR-T cell activity and behavior. Achieving safe, targeted, and efficient antitumor responses represents one of the key directions for the future development of CAR-T cell therapies.

国家自然科学基金项目（No. 82273207, No.82471378, No.82204541）