REVIEW article
Front. Immunol.
Sec. T Cell Biology
Smart Control of CAR-T Cells: Emerging Strategies for Safer and More Effective Cancer Immunotherapy
Provisionally accepted
- 1The 960th Hospital of the Chinese People's Liberation Army Joint Logistics Support Force, Jinan, China
- 2Zibo Central Hospital, Zibo, China
- 3960th Hospital of the PLA, Jinan, China
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Chimeric Antigen Receptor (CAR)-T cell therapy has developed cancer immunotherapy but remains restricted by severe toxicities, antigen escape, and loss of efficacy in solid tumors. Recent advances in smart control systems aim to enhance the safety and precision of CAR-T therapies through tunable, reversible, and context-dependent mechanisms. These include the importance of inducible CAR expression, logic-gated receptors, and external control systems using drugs, light, or biomaterials. Synthetic biology approaches integrating sensor circuits and feedback loops are paving the way for programmable immunity, enabling dynamic adjustment of CAR-T activity in real time. The aim of this study is to review recent advances in strategies that enable smart controlled and designed activity of CAR-T cells for safer and more effective cancer immunotherapy. It seeks to summarize key molecular, genetic, and synthetic approaches designed to regulate CAR-T cell activation, persistence, and cytotoxicity with high precision.
Keywords: antigen escape, cancer immunotherapy, CAR-T cells, cytokine release syndrome, logic gating, safety switches, Smart control, Tumor Microenvironment
Received: 14 Nov 2025; Accepted: 27 Jan 2026.
Copyright: © 2026 Zhang, Wang and Zhou. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Fang Zhou
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