嵌合抗原受体 (CAR) T 细胞疗法在血液恶性肿瘤患者中实现持久且潜在的治愈反应方面取得了巨大成功。 CAR 是定制的融合蛋白，可引导 T 细胞针对肿瘤细胞上的特定抗原，从而引发靶向免疫反应。几种靶向 CD19 的 CAR T 细胞疗法的批准导致涉及 CAR T 细胞疗法治疗血液恶性肿瘤的临床试验显着激增。尽管在理解与 CAR T 细胞疗法相关的反应机制、耐药模式和不良事件方面取得了进展，但将这些见解转化为强大的临床疗效在临床试验和现实场景中都显示出有限的结果。因此，通过严格的临床前研究评估 CAR T 细胞功能在完善临床应用治疗策略方面发挥着关键作用。本综述概述了用于评估 CAR T 细胞功能的各种体外和动物模型。我们讨论了涉及已批准的 CAR T 细胞产品的临床前研究的结果，以及最近旨在优化 CAR T 细胞功能的临床前研究的影响。该综述强调了稳健的临床前评估的重要性，以及对准确复制人类疾病的模型的需求，以弥合临床前成功和临床疗效之间的差距。版权所有 © 2024。由 Elsevier Ltd 出版。

Chimeric antigen receptor (CAR) T-cell therapy has achieved significant success in achieving durable and potentially curative responses in patients with hematological malignancies. CARs are tailored fusion proteins that direct T cells to a specific antigen on tumor cells thereby eliciting a targeted immune response. The approval of several CD19-targeted CAR T-cell therapies has resulted in a notable surge in clinical trials involving CAR T cell therapies for hematological malignancies. Despite advancements in understanding response mechanisms, resistance patterns, and adverse events associated with CAR T-cell therapy, the translation of these insights into robust clinical efficacy has shown modest outcomes in both clinical trials and real-world scenarios. Therefore, the assessment of CAR T-cell functionality through rigorous preclinical studies plays a pivotal role in refining therapeutic strategies for clinical applications. This review provides an overview of the various in vitro and animal models used to assess the functionality of CAR T-cells. We discuss the findings from preclinical research involving approved CAR T-cell products, along with the implications derived from recent preclinical studies aiming to optimize the functionality of CAR T-cells. The review underscores the importance of robust preclinical evaluations and the need for models that accurately replicate human disease to bridge the gap between preclinical success and clinical efficacy.Copyright © 2024. Published by Elsevier Ltd.