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.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:CAR-T cell therapy for hematological malignancies: Limitations and optimization strategies.
CAR-T cell therapy for hematological malignancies: Limitations and optimization strategies.
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在过去十年中,嵌合抗原受体(CAR)T细胞疗法的出现引领了一场针对多种癌症的细胞免疫治疗革命。尽管CAR-T 细胞疗法对某些B细胞驱动的血液系统恶性肿瘤患者已展现出显著疗效,但仍需进一步研究以拓宽CAR-T 细胞疗法在其他血液系统恶性肿瘤中的应用。此外,仍有相当比例的患者出现治疗失败。癌细胞上的CAR抗原丢失是癌症复发最常见的原因之一。此外,免疫逃逸可因不利的免疫抑制性肿瘤微环境以及CAR-T 细胞体内持久性受损而产生。除直接抗肿瘤活性外,CAR-T 细胞疗法相关的不良反应是治疗期间的另一主要关注点。作为一种新出现的治疗方法,近年来大量新的临床前研究提出了不同策略以增强疗效并减轻CAR-T 细胞相关毒性。本文综述了在CAR-T 细胞治疗期间阻碍血液系统恶性肿瘤患者获得良好疗效的主要障碍,以及为克服这些障碍所取得的最新进展。
In the past decade, the emergence of chimeric antigen receptor (CAR) T-cell therapy has led to a cellular immunotherapy revolution against various cancers. Although CAR-T cell therapies have demonstrated remarkable efficacy for patients with certain B cell driven hematological malignancies, further studies are required to broaden the use of CAR-T cell therapy against other hematological malignancies.
Moreover, treatment failure still occurs for a significant proportion of patients. CAR antigen loss on cancer cells is one of the most common reasons for cancer relapse.
Additionally, immune evasion can arise due to the hostile immunosuppressive tumor microenvironment and the impaired CAR-T cells in vivo persistence. Other than direct antitumor activity, the adverse effects associated with CAR-T cell therapy are another major concern during treatment.
As a newly emerged treatment approach, numerous novel preclinical studies have proposed different strategies to enhance the efficacy and attenuate CAR-T cell associated toxicity in recent years. The major obstacles that impede promising outcomes for patients with hematological malignancies during CAR-T cell therapy have been reviewed herein, along with recent advancements being made to surmount them.
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