Chimeric antigen receptor (CAR) T cell therapy, together with checkpoint inhibition, has been celebrated as a breakthrough technology due to the substantial benefit observed in clinical trials with patients suffering from relapsed or refractory B-cell malignancies. In this review, we provide a comprehensive overview of the clinical trials performed so far worldwide and analyze parameters such as targeted antigen and indication, CAR molecular design, CAR T cell manufacturing, anti-tumor activities, and related toxicities. More than 200 CAR T cell clinical trials have been initiated so far, most of which aim to treat lymphoma or leukemia patients using CD19-specific CARs. An increasing number of studies address solid tumors as well. Notably, not all clinical trials conducted so far have shown promising results. Indeed, in a few patients CAR T cell therapy resulted in severe adverse events with fatal outcome. Of note, less than 10% of the ongoing CAR T cell clinical trials are performed in Europe. Taking lead from our analysis, we discuss the problems and general hurdles preventing efficient clinical development of CAR T cells as well as opportunities, with a special focus on the European stage.

中文翻译：

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CAR T细胞的临床发展-挑战和翻译创新治疗方案的机会。

嵌合抗原受体（CAR）T细胞疗法与检查点抑制技术一起被誉为一项突破性技术，因为在临床试验中发现患有复发性或难治性B细胞恶性肿瘤的患者受益匪浅。在这篇综述中，我们提供了迄今为止在全球范围内进行的临床试验的全面概述，并分析了诸如靶向抗原和适应症，CAR分子设计，CAR T细胞制造，抗肿瘤活性以及相关毒性等参数。迄今为止，已经开展了200多次CAR T细胞临床试验，其中大多数旨在使用CD19特异性CARs治疗淋巴瘤或白血病患者。越来越多的研究也针对实体瘤。值得注意的是，到目前为止，并不是所有的临床试验都显示出令人满意的结果。的确，在少数患者中，CAR T细胞疗法导致严重的不良事件，并具有致命的后果。值得注意的是，正在进行的CAR T细胞临床试验中只有不到10％在欧洲进行。从我们的分析中带头，我们讨论了阻碍CAR T细胞有效临床发展的问题和普遍障碍以及机遇，特别是在欧洲阶段。