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:The Spectrum of CAR Cellular Effectors: Modes of Action in Anti-Tumor Immunity.
The Spectrum of CAR Cellular Effectors: Modes of Action in Anti-Tumor Immunity.
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CAR-T 细胞引领了过继性细胞治疗领域,并在治疗血液系统肿瘤方面显示出显著成果。由于实体瘤与血液系统肿瘤的生物学特性不同,CAR-T 细胞的缓解率尚未能转化至实体瘤。CAR工程已加入共刺激结构域、转基因细胞因子和开关受体,以提高在恶劣肿瘤微环境中的性能和持久性,但由于CAR-T 细胞固有的细胞类型局限性,包括HLA不相容、毒性(细胞因子释放综合征、神经毒性)以及由于自体细胞制备过程在物流上的挑战而导致的高成本,替代免疫细胞的使用正获得越来越多的关注。不需要HLA相容性的NK细胞和T细胞,或具有额外特性(如吞噬作用或抗原呈递)的巨噬细胞和树突状细胞,正日益被视为具有应用潜力的细胞载体。由于这些细胞具有不同的特性,临床医生和研究人员需要透彻理解它们的特殊性和共性。本综述将比较这些不同的细胞类型及其在CAR激活后所表现出的特定作用模式。
Chimeric antigen receptor-T cells have spearheaded the field of adoptive cell therapy and have shown remarkable results in treating hematological neoplasia. Because of the different biology of solid tumors compared to hematological tumors, response rates of CAR-T cells could not be transferred to solid entities yet. CAR engineering has added co-stimulatory domains, transgenic cytokines and switch receptors to improve performance and persistence in a hostile tumor microenvironment, but because of the inherent cell type limitations of CAR-T cells, including HLA incompatibility, toxicities (cytokine release syndrome, neurotoxicity) and high costs due to the logistically challenging preparation process for autologous cells, the use of alternative immune cells is gaining traction.
NK cells and T cells that do not need HLA compatibility or macrophages and dendritic cells with additional properties such as phagocytosis or antigen presentation are increasingly seen as cellular vehicles with potential for application. As these cells possess distinct properties, clinicians and researchers need a thorough understanding of their peculiarities and commonalities. This review will compare these different cell types and their specific modes of action seen upon CAR activation.
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