T细胞治疗策略，从同种异体干细胞移植到基因改造T细胞输注，具有强大的抗肿瘤作用，但往往伴随着副作用，其疗效有时仍有待提高。因此，提供灵活且易于可逆的基因表达调控系统来控制 T 细胞活性显得很重要。我们开发了一种基因表达调控技术，该技术利用生理学 GCN2-ATF4 途径诱导 T 细胞基因表达的能力，以响应一种必需氨基酸的缺乏。我们首先通过报告基因的瞬时表达证明了 NUTRIREG 在人类 T 细胞中的功能。然后我们验证了 NUTRIREG 可用于人类 T 细胞瞬时表达 IL-10 等治疗基因。总体而言，我们的结果为 NUTRIREG 以可逆方式调节人类 T 细胞转基因表达的前景奠定了坚实的基础，更广泛地说，为细胞免疫治疗策略中的众多预防性或治疗性治疗可能性奠定了坚实的基础。© 2023 作者。 HLA：免疫反应遗传学，约翰·威利 (John Wiley) 出版

T cell therapy strategies, from allogeneic stem cell transplantation toward genetically-modified T cells infusion, develop powerful anti-tumor effects but are often accompanied by side effects and their efficacy remains sometimes to be improved. It therefore appears important to provide a flexible and easily reversible gene expression regulation system to control T cells activity. We developed a gene expression regulation technology that exploits the physiological GCN2-ATF4 pathway's ability to induce gene expression in T cells in response to one essential amino acid deficiency. We first demonstrated the functionality of NUTRIREG in human T cells by transient expression of reporter genes. We then validated that NUTRIREG can be used in human T cells to transiently express a therapeutic gene such as IL-10. Overall, our results represent a solid basis for the promising use of NUTRIREG to regulate transgene expression in human T cells in a reversible way, and more generally for numerous preventive or curative therapeutic possibilities in cellular immunotherapy strategies.© 2023 The Authors. HLA: Immune Response Genetics published by John Wiley & Sons Ltd.