Signaling Research Centres BIOSS and CIBSS; Department of Immunology, Faculty of Biology, University of Freiburg, Freiburg, Germany.
Department of Immunology, Faculty of Biology, University of Freiburg, Freiburg, Germany.
Eur J Immunol. 2024 Nov;54(11):e2451074. doi: 10.1002/eji.202451074. Epub 2024 Aug 27.
Recent years have witnessed the success of αβ T cells engineered to express chimeric antigen receptors (CARs) in treating haematological cancers. CARs combine the tumour antigen binding capability of antibodies with the signalling functions of the T-cell receptor (TCR) ζ chain and co-stimulatory receptors. Despite the success, αβ CAR T cells face limitations. Possible solutions would be the use of γδ T cells and new chimeric receptors, such as TCR fusion constructs (TRuCs). Notably, γδ CAR T cells are gaining traction in pre-clinical and clinical studies, demonstrating a promising safety profile in several pilot studies. This review delves into the current understanding of γδ CAR and TCR fusion construct T cells, exploring the opportunities and challenges they present for cancer treatment.
近年来,经基因工程改造表达嵌合抗原受体(CAR)的αβ T 细胞在治疗血液系统癌症方面取得了成功。CAR 结合了抗体对肿瘤抗原的结合能力和 T 细胞受体(TCR)ζ 链及共刺激受体的信号转导功能。尽管取得了成功,但αβ CAR T 细胞仍面临一些限制。可能的解决方案是使用 γδ T 细胞和新型嵌合受体,如 TCR 融合构建体(TRuCs)。值得注意的是,γδ CAR T 细胞在临床前和临床研究中受到关注,在几项初步研究中显示出有前景的安全性特征。本文深入探讨了当前对 γδ CAR 和 TCR 融合构建体 T 细胞的理解,探索了它们在癌症治疗方面带来的机遇和挑战。