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:Preclinical Evaluation of CAR T Cell Function: In Vitro and In Vivo Models.
Preclinical Evaluation of CAR T Cell Function: In Vitro and In Vivo Models.
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利用嵌合抗原受体(CAR)T细胞的免疫治疗是一种迅速兴起的治疗模式,通过工程化改造T细胞以重定向肿瘤特异性细胞毒性。CAR-T 细胞在B细胞恶性肿瘤中的疗效已得到充分表征,并在其他类型肿瘤中进行了严格研究。CAR-T 细胞功能的临床前评估,包括直接杀伤肿瘤、细胞因子产生和记忆反应,对于CAR-T 细胞疗法的开发和优化至关重要。此类全面检查通常在不同类型的模型中进行。模型建立应聚焦于临床环境中的关键挑战,以及生成可靠数据以指示CAR-T 细胞临床治疗效力的能力。此外,模拟CAR-T 细胞与肿瘤微环境之间的相互作用,为未来增强疗效的努力提供了额外见解,尤其是针对实体瘤。本综述将总结用于CAR-T 细胞功能评估的体外和体内模型,包括它们如何随着CAR-T 细胞研究的需求而演变、它们能为CAR-T 细胞产品的临床前评估提供哪些信息,以及近期在更贴近临床的模型中测试CAR-T 细胞的技术进展。
Immunotherapy using chimeric antigen receptor (CAR) T cells is a rapidly emerging modality that engineers T cells to redirect tumor-specific cytotoxicity. CAR T cells have been well characterized for their efficacy against B cell malignancies, and rigorously studied in other types of tumors.
Preclinical evaluation of CAR T cell function, including direct tumor killing, cytokine production, and memory responses, is crucial to the development and optimization of CAR T cell therapies. Such comprehensive examinations are usually performed in different types of models. Model establishment should focus on key challenges in the clinical setting and the capability to generate reliable data to indicate CAR T cell therapeutic potency in the clinic.
Further, modeling the interaction between CAR T cells and tumor microenvironment provides additional insight for the future endeavors to enhance efficacy, especially against solid tumors. This review will summarize both in vitro and in vivo models for CAR T cell functional evaluation, including how they have evolved with the needs of CAR T cell research, the information they can provide for preclinical assessment of CAR T cell products, and recent technology advances to test CAR T cells in more clinically relevant models.
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