嵌合抗原受体 T 细胞 (CAR-T) 的出现带来了癌症免疫治疗的范式转变，在越来越多的恶性肿瘤中取得了显着的疗效。虽然 CAR-T 对多种疾病非常有效，可以挽救那些被认为无法治愈的患者，但它们具有独特的毒性，可能危及生命。了解这些毒性的生物学和风险因素有助于制定有针对性的治疗方法，从而成功减轻这些毒性。特别令人感兴趣的三种毒性是细胞因子释放综合征（CRS）、免疫效应细胞相关神经毒性综合征（ICANS）和免疫效应细胞相关噬血细胞淋巴组织细胞增多症（HLH）样综合征（IEC-HS）。每一种疾病的特征都是细胞因子风暴和过度炎症。然而，它们在驱动病理生理学的细胞因子和免疫细胞方面存在机制上的不同。我们总结了 CAR-T 相关毒性领域的现状，重点关注基础生物学及其如何为毒性管理和预防提供信息。我们还重点介绍了几种在临床前模型和临床中显示出前景的新兴药物。许多已建立的和新兴的药物似乎不会影响 CAR-T 的抗肿瘤功能，从而为更多和更广泛的 CAR-T 应用打开了大门。© 2024。作者。

The advent of chimeric antigen receptor T cells (CAR-T) has been a paradigm shift in cancer immunotherapeutics, with remarkable outcomes reported for a growing catalog of malignancies. While CAR-T are highly effective in multiple diseases, salvaging patients who were considered incurable, they have unique toxicities which can be life-threatening. Understanding the biology and risk factors for these toxicities has led to targeted treatment approaches which can mitigate them successfully. The three toxicities of particular interest are cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and immune effector cell-associated hemophagocytic lymphohistiocytosis (HLH)-like syndrome (IEC-HS). Each of these is characterized by cytokine storm and hyperinflammation; however, they differ mechanistically with regard to the cytokines and immune cells that drive the pathophysiology. We summarize the current state of the field of CAR-T-associated toxicities, focusing on underlying biology and how this informs toxicity management and prevention. We also highlight several emerging agents showing promise in preclinical models and the clinic. Many of these established and emerging agents do not appear to impact the anti-tumor function of CAR-T, opening the door to additional and wider CAR-T applications.© 2024. The Author(s).