BIH Center for Regenerative Therapies (BCRT) and Berlin Center for Advanced Therapies (BeCAT), Charité-Universitätsmedizin Berlin and Berlin Institute of Health (BIH), Berlin, Germany.
INSERM, Centre de Recherche en Transplantation et Immunologie, UMR 1064, ITUN, Nantes, France.
Front Immunol. 2021 Feb 24;11:611638. doi: 10.3389/fimmu.2020.611638. eCollection 2020.
Regulatory Tcells (Treg) are essential components of peripheral immune homeostasis. Adoptive Treg cell therapy has shown efficacy in a variety of immune-mediated diseases in preclinical studies and is now moving from phase I/IIa to larger phase II studies aiming to demonstrate efficacy. However, hurdles such as stability and efficacy remain to be addressed. Nevertheless, preclinical models have shown that Treg function and specificity can be increased by pharmacological substances or gene modifications, and even that conventional T cells can be converted to Treg potentially providing new sources of Treg and facilitating Treg cell therapy. The exponential growth in genetic engineering techniques and their application to T cells coupled to a large body of knowledge on Treg open numerous opportunities to generate Treg with "superpowers". This review summarizes the genetic engineering techniques available and their applications for the next-generation of Super-Treg with increased function, stability, redirected specificity and survival.
调节性 T 细胞（Treg）是外周免疫稳态的重要组成部分。在临床前研究中，过继性 Treg 细胞治疗已显示出在多种免疫介导性疾病中的疗效，目前正在从 I/IIa 期向更大规模的 II 期研究推进，旨在证明疗效。然而，稳定性和疗效等障碍仍有待解决。尽管如此，临床前模型表明，Treg 的功能和特异性可以通过药理物质或基因修饰来提高，甚至可以将常规 T 细胞转化为 Treg，这可能为 Treg 提供新的来源，并促进 Treg 细胞治疗。基因工程技术的指数级增长及其在 T 细胞中的应用，加上大量关于 Treg 的知识，为生成具有“超能力”的 Treg 提供了众多机会。这篇综述总结了现有的基因工程技术及其在下一代具有增强功能、稳定性、重定向特异性和生存能力的 Super-Treg 中的应用。
