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:Chimeric antigen receptor-immune cells against solid tumors: Structures, mechanisms, recent advances, and future developments.
Chimeric antigen receptor-immune cells against solid tumors: Structures, mechanisms, recent advances, and future developments.
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嵌合抗原受体(CAR)T 细胞免疫疗法的出现,推动了血液系统恶性肿瘤治疗取得突破,但用于治疗实体瘤的效果有限。与 CAR-T 细胞相比,CAR-自然杀伤(NK)细胞具有若干优势:可使用现成细胞系或主要组织相容性复合体(MHC)不匹配的异体 NK 细胞制备,因此更可能成为“现成型”产品。
此外,CAR-NK 细胞既可通过 CAR 依赖途径,也可通过 CAR 非依赖途径杀伤癌细胞,且毒性有限。巨噬细胞是人体中可塑性最强的免疫细胞,能够高效浸润肿瘤,并大量存在于肿瘤微环境(TME)中。
值得注意的是,CAR-巨噬细胞(CAR-M)近期在数种实体瘤中取得令人振奋的临床前结果。尽管如此,CAR-T、CAR-NK 和 CAR-M 各有优势与局限。本综述从五个方面系统讨论 CAR-T、CAR-NK 和 CAR-M 的现状、进展及主要障碍:CAR 结构、治疗机制、最新研究进展、当前挑战与解决方案,以及基于现有研究的比较,以期为未来实体瘤治疗提供合理选择。
The advent of chimeric antigen receptor (CAR)-T cell immunotherapies has led to breakthroughs in the treatment of hematological malignancies.
However, their success in treating solid tumors has been limited. CAR-natural killer (NK) cells have several advantages over CAR-T cells because NK cells can be made from pre-existing cell lines or allogeneic NK cells with a mismatched major histocompatibility complex (MHC), which means they are more likely to become an "off-the-shelf" product.
Moreover, they can kill cancer cells via CAR-dependent/independent pathways and have limited toxicity. Macrophages are the most malleable immune cells in the body. These cells can efficiently infiltrate into tumors and are present in large numbers in tumor microenvironments (TMEs).
Importantly, CAR-macrophages (CAR-Ms) have recently yielded exciting preclinical results in several solid tumors. Nevertheless, CAR-T, CAR-NK, and CAR-M all have their own advantages and limitations.
In this review, we systematically discuss the current status, progress, and the major hurdles of CAR-T cells, CAR-NK cells, and CAR-M as they relate to five aspects: CAR structure, therapeutic mechanisms, the latest research progress, current challenges and solutions, and comparison according to the existing research in order to provide a reasonable option for treating solid tumors in the future.
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