Background

Chimeric antigen receptor (CAR)-modified T cell therapy has shown great potential in the immunotherapy of patients with hematologic malignancies. In spite of this striking achievement, there are still major challenges to overcome in CAR T cell therapy of solid tumors, including treatment-related toxicity and specificity. Also, other obstacles may be encountered in tackling solid tumors, such as their immunosuppressive microenvironment, the heterogeneous expression of cell surface markers, and the cumbersome arrival of T cells at the tumor site. Although several strategies have been developed to overcome these challenges, aditional research aimed at enhancing its efficacy with minimum side effects, the design of precise yet simplified work flows and the possibility to scale-up production with reduced costs and related risks is still warranted.

Conclusions

Here, we review main strategies to establish a balance between the toxicity and activity of CAR T cells in order to enhance their specificity and surpass immunosuppression. In recent years, many clinical studies have been conducted that eventually led to approved products. To date, the FDA has approved two anti-CD19 CAR T cell products for non-Hodgkin lymphoma therapy, i.e., axicbtagene ciloleucel and tisagenlecleucel. With all the advances that have been made in the field of CAR T cell therapy for hematologic malignancies therapy, ongoing studies are focused on optimizing its efficacy and specificity, as well as reducing the side effects. Also, the efforts are poised to broaden CAR T cell therapeutics for other cancers, especially solid tumors.

中文翻译：

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CAR T 细胞疗法作为癌症免疫疗法的一种有前景的方法：挑战与机遇

背景

嵌合抗原受体 (CAR) 修饰的 T 细胞疗法在血液系统恶性肿瘤患者的免疫治疗中显示出巨大的潜力。尽管取得了这一惊人的成就，但实体瘤的 CAR T 细胞治疗仍存在重大挑战需要克服，包括治疗相关的毒性和特异性。此外，在处理实体瘤时可能会遇到其他障碍，例如它们的免疫抑制微环境、细胞表面标志物的异质表达以及 T 细胞到达肿瘤部位的麻烦。尽管已经开发了多种策略来克服这些挑战，但旨在以最小副作用提高其功效的额外研究、精确而简化的工作流程的设计以及在降低成本和相关风险的情况下扩大生产的可能性仍然是必要的。

结论

在这里，我们回顾了在 CAR T 细胞的毒性和活性之间建立平衡以增强其特异性并超越免疫抑制的主要策略。近年来，进行了许多临床研究，最终导致产品获得批准。迄今为止，FDA已经批准了两种用于非霍奇金淋巴瘤治疗的抗CD19 CAR T细胞产品，即axicbtagene ciloleucel和tisagenlecleucel。随着用于血液系统恶性肿瘤治疗的 CAR T 细胞疗法领域取得的所有进展，正在进行的研究集中在优化其疗效和特异性，以及减少副作用上。此外，这些努力有望扩大 CAR T 细胞疗法对其他癌症，尤其是实体瘤的治疗。