Advancement in our understanding of immune cell recognition and emerging cellular engineering technologies during the last decades made active manipulation of the T cell response possible. Synthetic immunology is providing us with an expanding set of composite receptor molecules capable to reprogram immune cell function in a predefined fashion. Since the first prototypes in the late 1980s, the design of chimeric antigen receptors (CARs; T-bodies, immunoreceptors), has followed a clear line of stepwise improvements from antigen-redirected targeting to designed “living factories” delivering transgenic products on demand. Building on basic research and creative clinical exploration, CAR T cell therapy has been achieving spectacular success in the treatment of hematologic malignancies, now beginning to improve the outcome of cancer patients. In this study, we briefly review the history of CARs and outline how the progress in the basic understanding of T cell recognition and of cell engineering technologies made novel therapies possible.

中文翻译：

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以合成免疫学和 T 细胞工程为基础：嵌合抗原受体历史简史

在过去几十年中，我们对免疫细胞识别和新兴细胞工程技术的理解取得了进步，这使得主动操纵 T 细胞反应成为可能。合成免疫学为我们提供了一组扩展的复合受体分子，能够以预定义的方式重新编程免疫细胞功能。自 1980 年代后期的第一个原型以来，嵌合抗原受体（CAR；T 体、免疫受体）的设计遵循了一条清晰的逐步改进路线，从抗原重定向靶向到设计的“活工厂”按需提供转基因产品。基于基础研究和创造性临床探索，CAR T 细胞疗法在治疗血液系统恶性肿瘤方面取得了惊人的成功，现在开始改善癌症患者的预后。