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-NK cell therapy for hematological malignancies.
CAR-NK cell therapy for hematological malignancies.
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嵌合抗原受体(CAR)-自然杀伤(NK)细胞代表一种新型细胞治疗平台,与CAR-T 细胞的区别在于其更有利的安全性特征、更简便的现货型异体制造及由此带来的可扩展性,以及无需预先致敏的固有细胞毒性。来源于多种来源的CAR-NK细胞已在多项临床试验中用于对抗血液系统恶性肿瘤,显示出显著的治疗反应和疗效,且无严重不良反应。CAR-NK细胞疗法中正在解决的局限性包括NK细胞体内持久性方面的挑战、代谢瓶颈,以及诱导NK细胞耗竭的肿瘤利用的免疫抑制机制。本综述综合了CAR-NK细胞工程当前的趋势与创新,审视了临床环境中遇到的生物学和技术挑战,概述了正在实施的靶向临床前方法,并介绍了近期研发管线中的早期临床试验。总而言之,我们强调了CAR-NK细胞疗法治疗血液系统癌症的快速进展和变革性潜力。
Chimeric antigen receptor (CAR)-natural killer (NK) cells represent a novel cell therapy platform distinguished from CAR T cells by their more favorable safety profile, easier off-the-shelf allogeneic manufacturing and consequent scalability, and their innate cytotoxicity without needing previous sensitization. CAR-NK cells derived from a variety of sources have been used against hematologic malignancies in several clinical trials, showing significant therapeutic responses and efficacy without severe adverse effects.
Limitations that are being addressed in CAR-NK cell therapy include challenges regarding NK cell persistence in vivo, metabolic bottlenecks, and tumor-coopted immunosuppressive mechanisms that induce NK cell exhaustion.
This review synthesizes current trends and innovations in CAR-NK cell engineering, examines the biological and technical challenges encountered in the clinical setting, outlines targeted preclinical approaches being implemented, and introduces recent early phase clinical trials in the pipeline. Summatively, we highlight the rapidly advancing and transformative potential of CAR-NK cell therapy for treating hematological cancers.
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