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:Determinants of Chimeric Antigen Receptor (CAR) T Cell Success: In Vitro and In Vivo Preclinical Assessment.
Determinants of Chimeric Antigen Receptor (CAR) T Cell Success: In Vitro and In Vivo Preclinical Assessment.
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通过将传统实验方法与创新技术相结合,CAR-T 细胞领域有望产生更具临床相关性和预测性的数据,从而加速开发更安全、更有效和个性化的 CAR-T 细胞疗法。
本综述全面介绍评估 CAR-T 细胞功能和毒性的体外与体内临床前模型,考察传统实验方法及其局限,讨论新兴技术,并重点说明如何整合这些策略以推进未来 CAR-T 疗法。
体外实验可提供疗效信息,但无法模拟细胞迁移、动态免疫细胞相互作用和复杂肿瘤微环境。体内小鼠模型可进行更复杂的生理评估,但受物种差异限制。患者来源肿瘤类器官、器官芯片或多器官芯片微流控等下一代平台,正成为在生理相关情境下模拟 CAR-T 疗法的潜在工具;计算方法也日益用于开发新型 CAR 设计并预测患者应答。
通过整合传统实验方法和创新技术,CAR-T 领域有望产生更具临床相关性和预测性的证据,加速开发更安全、有效且个体化的 CAR-T 疗法。
This review provides a comprehensive overview of in vitro and in vivo preclinical modeling for CAR T cell functionality and toxicity assessment. We examine traditional experimental approaches and their limitations, discuss emerging technologies, and highlight how these strategies can be integrated to advance future CAR T cell therapies.
In vitro assays provide insights into efficacy but fail to model trafficking, dynamic immune cell interactions, and complex tumor microenvironments. In vivo mouse models allow for more complex physiological evaluation but are limited by species differences. Next generation platforms, such as patient-derived tumor organoids and organ- or multi-organ-on-a-chip microfluidics are emerging as potential tools to model CAR T cell therapy in physiologically relevant contexts and computational approaches are being increasingly used to develop novel CAR designs and predict patient responses.
By integrating traditional experimental approaches with innovative technologies, the CAR T cell field is poised to generate more clinically relevant and predictive data thereby accelerating the development of safer, more effective, and personalized CAR T cell therapies.
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