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.

中文翻译：

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CAR 驾驶座上的抗原结合部分

近几十年来，免疫肿瘤学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细胞疗法取得了惊人的成果。多年来，CAR-T 细胞的开发遵循了稳定的进化道路，重点是提高 T 细胞的效力和可持续性，从而产生了不同的 CAR 代。然而，对于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，是关于 CAR 中使用的靶向部分及其具体特性。最近，人们已经认识到优化该领域的重要性，并且已经开发了其可能性。在过去的 10 年里，除了基于 scFv 的经典 CAR 之外，还出现了单域 CAR、天然受体配体 CAR、通用 CAR 和针对多种抗原的 CAR。此外，正在检查靶向结构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。我们讨论了不同的形式，每种形式都有自己的优点和缺点，以及亲和力调节、亲合力效应、表位位置和细胞外间隔物的影响方面的发展。