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:Chimeric antigen receptor natural killer cells: a promising antitumor immunotherapy.
Chimeric antigen receptor natural killer cells: a promising antitumor immunotherapy.
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嵌合抗原受体(CAR)T细胞已成功用于恶性肿瘤的过继细胞治疗。然而,移植物抗宿主病和细胞因子释放综合征等副作用、治疗耐药、来源有限以及高成本等障碍限制了CAR-T 细胞的应用。近期,CAR自然杀伤(NK)细胞因具有较强的内在抗肿瘤活性且副作用相对较轻等优势,被用作过继免疫治疗的效应细胞。此外,CAR-NK细胞可由多种来源制备,且不需要严格的人类白细胞抗原匹配,因此有望成为临床应用的“现货型”产品。尽管CAR-NK细胞的应用受到增殖能力有限及其在免疫抑制性肿瘤微环境中效能受损的限制,但进一步优化CAR结构和联合治疗有望克服这些挑战。本综述总结CAR-NK细胞的研究进展、制备方式、临床治疗结局、领域挑战及可能解决方案,并讨论其他免疫细胞用于CAR工程改造的新兴应用。总体而言,本文将全面概述CAR-NK细胞治疗肿瘤的当前进展,并评估挑战和未来机遇。
Chimeric antigen receptor (CAR) T cells have been successfully used in adoptive cell therapy for malignancies.
However, some obstacles, including side effects such as graft-versus-host disease and cytokine release syndrome, therapy resistance, limited sources, as well as high cost, limited the application of CAR T cells. Recently, CAR natural killer (NK) cells have been pursued as the effector cells for adoptive immunotherapy for their attractive merits of strong intrinsic antitumor activity and relatively mild side effects.
Additionally, CAR NK cells can be available from various sources and do not require strict human leukocyte antigen matching, which suggests them as promising "off-the-shelf" products for clinical application. Although the use of CAR NK cells is restrained by the limited proliferation and impaired efficiency within the immunosuppressive tumor microenvironment, further investigation in optimizing CAR structure and combination therapies will overcome these challenges.
This review will summarize the advancement of CAR NK cells, CAR NK cell manufacture, the clinical outcomes of CAR NK therapy, the challenges in the field, and prospective solutions. Besides, we will discuss the emerging application of other immune cells for CAR engineering. Collectively, this comprehensive review will provide a valuable and informative summary of current progress and evaluate challenges and future opportunities of CAR NK cells in tumor treatment.
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