In Vivo Cellular and Molecular Imaging Laboratory, Vrije Universiteit Brussel, Brussels, Belgium.
Laboratory of Hematology and Immunology, Vrije Universiteit Brussel, Brussels, Belgium.
Med Res Rev. 2022 Jan;42(1):306-342. doi: 10.1002/med.21818. Epub 2021 May 24.
Immuno-oncology has been at the forefront of cancer treatment in recent decades. In particular immune checkpoint and chimeric antigen receptor (CAR)-T cell therapy have achieved spectacular results. Over the years, CAR-T cell development has followed a steady evolutionary path, focusing on increasing T cell potency and sustainability, which has given rise to different CAR generations. However, there was less focus on the mode of interaction between the CAR-T cell and the cancer cell; more specifically on the targeting moiety used in the CAR and its specific properties. Recently, the importance of optimizing this domain has been recognized and the possibilities have been exploited. Over the last 10 years-in addition to the classical scFv-based CARs-single domain CARs, natural receptor-ligand CARs, universal CARs and CARs targeting more than one antigen have emerged. In addition, the specific parameters of the targeting domain and their influence on T cell activation are being examined. In this review, we concisely present the history of CAR-T cell therapy, and then expand on various developments in the CAR ectodomain. We discuss different formats, each with their own advantages and disadvantages, as well as the developments in affinity tuning, avidity effects, epitope location, and influence of the extracellular spacer.
免疫肿瘤学在近几十年来一直处于癌症治疗的前沿。特别是免疫检查点和嵌合抗原受体 (CAR)-T 细胞疗法已经取得了显著的效果。多年来，CAR-T 细胞的发展一直遵循着稳定的进化路径，专注于提高 T 细胞的效力和持久性，从而产生了不同的 CAR 代次。然而，人们对 CAR-T 细胞与癌细胞之间的相互作用模式关注较少；更具体地说，对 CAR 中使用的靶向部分及其特定性质关注较少。最近，人们已经认识到优化这一领域的重要性，并已经开始利用这一领域的可能性。在过去的 10 年中，除了基于经典 scFv 的 CAR 外，单域 CAR、天然受体-配体 CAR、通用 CAR 以及靶向多个抗原的 CAR 也相继出现。此外，还在研究靶向域的具体参数及其对 T 细胞激活的影响。在这篇综述中，我们简要介绍了 CAR-T 细胞疗法的历史，然后扩展了 CAR 胞外域的各种发展。我们讨论了不同的格式，每种格式都有其自身的优点和缺点，以及亲和力调谐、亲合力效应、表位位置和细胞外间隔区的影响的发展。
