A Critical Review of CAR-T Therapies for Glioblastoma: What's Wrong with the Current Attempts?

Sergei V Belokon, Valeriya A Kukarskaya, Ilya D Klabukov, Victoria A Shestakova, Sergei A Ivanov, Petr V Shegay, Andrei D Kaprin, Denis S Baranovskii
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Abstract

Today, CAR-T therapy has been widely acknowledged as a "gold standard" treatment for certain hematologic diseases. There is a relatively small but enhancing body of clinical trials studying the effectiveness of CAR-T in treating glioblastoma, known as the most common and aggressive brain tumor in adults. Despite the promising findings, currently available data is still erratic. We aimed to overview the recent clinical attempts to apply CAR-T therapy as the treatment strategy for glioblastoma and highlight non-obvious problems occurring: flaws in the study design with suspicious inclusion criteria, absence of narrow nosologic focus, poor validation or even nonvalid imaging technologies and inconveniencing efficacy evaluation. We also discussed further upcoming advanced approaches for CAR-T cell manufacturing. We are convinced that our review could help to define the right place for CAR-T therapy in glioblastoma treatment strategy and would pave the way for future successful clinical trials.

CAR-T治疗胶质母细胞瘤的重要回顾:目前的尝试有什么问题?
如今,CAR-T疗法已被广泛认为是治疗某些血液病的“黄金标准”。CAR-T治疗胶质母细胞瘤是成人中最常见、最具侵袭性的脑肿瘤,目前研究CAR-T治疗胶质母细胞瘤有效性的临床试验相对较少,但正在不断增强。尽管有了令人鼓舞的发现,但目前可用的数据仍然不稳定。我们的目的是概述最近临床尝试将CAR-T疗法作为胶质母细胞瘤的治疗策略,并强调出现的一些不明显的问题:研究设计存在缺陷,纳入标准可疑,缺乏狭窄的病理焦点,验证性差甚至无效的成像技术以及不方便的疗效评估。我们还讨论了CAR-T细胞制造的进一步先进方法。我们相信我们的综述可以帮助确定CAR-T疗法在胶质母细胞瘤治疗策略中的正确位置,并为未来成功的临床试验铺平道路。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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