CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Overcoming chimeric antigen receptor-T (CAR-T) resistance with checkpoint inhibitors: Existing methods, challenges, clinical success, and future prospects : A comprehensive review.
Overcoming chimeric antigen receptor-T (CAR-T) resistance with checkpoint inhibitors: Existing methods, challenges, clinical success, and future prospects : A comprehensive review.
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免疫检查点阻断是迄今为止最成功的癌症免疫治疗形式,美国超过43%的癌症患者有资格接受该治疗;然而,仅有至多12.5%的患者对其产生应答。同样,使用生物工程化CAR-T(CAR-T)细胞和T细胞受体(TCR)细胞的过继细胞疗法对液体肿瘤提供了极好的应答,但这两种免疫治疗形式在肿瘤微环境中都遇到了挑战,该微环境既缺乏肿瘤特异性T细胞,又对外部给予的CAR-T 和TCR细胞具有强烈的免疫抑制作用。本综述侧重于在生物学和临床层面理解已获批的检查点阻断和过继细胞疗法,然后深入探讨它们的联合如何以及为何在克服各自缺点方面具有重大前景。下一代检查点抑制剂的出现进一步加强了免疫检查点领域,一个专门章节探讨了这些抑制剂如何能够解决将检查点阻断与过继细胞疗法联合时存在的障碍,并聚焦于我们的癌症靶点以实现长期免疫。
Immune checkpoint blockade is, as of today, the most successful form of cancer immunotherapy, with more than 43 % of cancer patients in the US eligible to receive it; however, only up to 12. 5 % of patients respond to it. Similarly, adoptive cell therapy using bioengineered chimeric antigen receptorT (CAR-T) cells and T-cell receptor (TCR) cells has provided excellent responses against liquid tumours, but both forms of immunotherapy have encountered challenges within a tumour microenvironment that is both lacking in tumour-specific T-cells and is strongly immunosuppressive toward externally administered CAR-T and TCR cells.
This review focuses on understanding approved checkpoint blockade and adoptive cell therapy at both biological and clinical levels before delving into how and why their combination holds significant promise in overcoming their individual shortcomings. The advent of next-generation checkpoint inhibitors has further strengthened the immune checkpoint field, and a special section explores how these inhibitors can address existing hurdles in combining checkpoint blockade with adoptive cell therapy and homing in on our cancer target for long-term immunity.
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