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Opportunities and challenges of "remote-controlling" CAR-T cells for tumor therapy
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Abstract:
[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.
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