肿瘤细胞治疗研究
英文原题：Forks in the road for CAR T and CAR NK cell cancer therapies.
嵌合抗原受体（CAR）T 细胞疗法的出现，使儿童和成人复发/难治性血液系统恶性肿瘤患者获得了前所未有的长期清除。
嵌合抗原受体（CAR）T细胞疗法问世后，儿童和成人复发/难治性血液系统恶性肿瘤患者均实现了前所未有的长期缓解。然而，CAR-T相关的细胞因子释放综合征和神经毒性等严重毒性影响其治疗效用；此外，治疗实体瘤的疗效仍不理想。因此，研究者开始采用工程改造策略调整其他免疫细胞类型，尤其是自然杀伤（NK）细胞。CAR-NK细胞具有CAR依赖和CAR非依赖（先天免疫介导）的抗肿瘤杀伤能力，其细胞毒作用不受主要组织相容性复合体限制，异体反应风险较低，且缺乏CAR-T的主要毒性，因此成为有前景的下一代CAR免疫细胞之一，也适用于“现货型”治疗。本综述比较CAR-T与CAR-NK细胞疗法，重点讨论免疫突触、工程改造策略及其挑战。
The advent of chimeric antigen receptor (CAR) T cell therapy has resulted in unprecedented long-term clearance of relapse/refractory hematological malignancies in both pediatric and adult patients. However, severe toxicities, such as cytokine release syndrome and neurotoxicity, associated with CAR T cells affect therapeutic utility; and treatment efficacies for solid tumors are still not impressive. As a result, engineering strategies that modify other immune cell types, especially natural killer (NK) cells have arisen. Owing to both CAR-dependent and CAR-independent (innate immune-mediated) antitumor killing capacity, major histocompatibility complex-independent cytotoxicity, reduced risk of alloreactivity and lack of major CAR T cell toxicities, CAR NK cells constitute one of the promising next-generation CAR immune cells that are also amenable as 'off-the-shelf' therapeutics. In this Review, we compare CAR T and CAR NK cell therapies, with particular focus on immunological synapses, engineering strategies and challenges.
MEMBER ACCOUNT
登录成功会直接打开下一页。
