Sebe Attila, Anliker Brigitte, Rau Juliane, Renner Matthias
Abteilung Medizinische Biotechnologie, Paul-Ehrlich-Institut, Paul-Ehrlich-Str. 51-59, 63225, Langen, Deutschland.
Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz. 2020 Nov;63(11):1403-1411. doi: 10.1007/s00103-020-03230-8. Epub 2020 Oct 16.
Adoptive T‑cell therapies are emerging tools to combat various human diseases. CAR‑T cells are approved and marketed as last line therapeutics in advanced B‑cell lymphomas and leukemias. TCR-engineered T cells are being evaluated in clinical trials for a variety of hematological and solid tumors. Genetically modified regulatory T cells, however, are still in the initial stages of clinical development for the induction of immune tolerance in various indications.Here we outline the general role of regulatory T cells in establishing self-tolerance and the mechanisms by which these suppress the effector immune cells. Further, the role of regulatory T cells in the pathomechanism of certain immune diseases is presented, and the current status of clinical developments of genetically modified Treg cells is discussed. We also present the regulatory framework for genetically modified regulatory T cells as advanced therapy medicinal products, including aspects of manufacture and quality control, as well as nonclinical and clinical development requirements.
过继性T细胞疗法是对抗各种人类疾病的新兴工具。嵌合抗原受体T细胞（CAR-T细胞）已被批准作为晚期B细胞淋巴瘤和白血病的最后一线治疗药物上市。工程化T细胞受体（TCR）的T细胞正在针对多种血液系统肿瘤和实体瘤进行临床试验评估。然而，基因改造的调节性T细胞仍处于临床开发的初始阶段，用于在各种适应症中诱导免疫耐受。在此，我们概述调节性T细胞在建立自身耐受中的一般作用以及这些细胞抑制效应免疫细胞的机制。此外，还介绍了调节性T细胞在某些免疫疾病发病机制中的作用，并讨论了基因改造的调节性T细胞的临床开发现状。我们还介绍了作为先进治疗药品的基因改造调节性T细胞的监管框架，包括生产和质量控制方面，以及非临床和临床开发要求。
