Adoptive transfer of allogeneic and genetically modified T cells, such as CAR-T and TCR-T cells, can induce profound immune reactivity against cancer tissue. At the same time, these therapies are associated with severe off-target and on-target toxicities. For this reason, the development of genetic safety switches that can be used to control the activity of T cells in vivo has become an active field of research. With the spectrum of technologies developed, reversible control of cell products either by supply or removal of small molecules, by supply of protein-based regulators, or by physical stimuli such as light, ultrasound or heat, has become feasible. In this review, we describe the mechanistic classes of genetic safety switches, such as transcription-based or protein-based control of antigen receptors, split receptors, small molecule responsive antibodies, as well as universal remote controls, and discuss their advantages and limitations.

同种异体和转基因 T 细胞（如 CAR-T 和 TCR-T 细胞）的过继转移可以诱导针对癌组织的深刻免疫反应。同时，这些疗法与严重的脱靶和靶向毒性有关。出于这个原因，可用于控制体内T 细胞活性的基因安全开关的开发已成为一个活跃的研究领域。随着一系列技术的发展，通过供应或去除小分子、供应基于蛋白质的调节剂或通过光、超声波或热等物理刺激对细胞产品进行可逆控制已变得可行。在这篇综述中，我们描述了基因安全开关的机械类别，例如基于转录或基于蛋白质的抗原受体控制、分裂受体、小分子响应抗体以及通用遥控器，并讨论了它们的优点和局限性。