Riding the storm: managing cytokine-related toxicities in CAR-T cell therapy.

IF 7.9 2区 医学 Q1 IMMUNOLOGY Seminars in Immunopathology Pub Date : 2024-07-16 DOI:10.1007/s00281-024-01013-w
Andrew D Hughes, David T Teachey, Caroline Diorio
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Abstract

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.

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乘风破浪:CAR-T 细胞疗法中细胞因子相关毒性的管理。
嵌合抗原受体 T 细胞(CAR-T)的出现推动了癌症免疫疗法的范式转变,据报道,它对越来越多的恶性肿瘤取得了显著疗效。虽然 CAR-T 对多种疾病都非常有效,能挽救被认为无法治愈的患者,但它们也有独特的毒性,可能会危及生命。通过对这些毒性的生物学特性和风险因素的了解,我们找到了可以成功缓解这些毒性的靶向治疗方法。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嗜血细胞淋巴组织细胞增多症(HLH)样综合征(IEC-HS)这三种毒性反应尤其值得关注。它们都以细胞因子风暴和炎症亢进为特征;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理上的差异。我们总结了CAR-T相关毒性领域的现状,重点是潜在的生物学以及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大有可为的新兴药物。其中许多成熟的和新兴的药物似乎不会影响 CAR-T 的抗肿瘤功能,这为更多更广泛的 CAR-T 应用打开了大门。
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来源期刊
Seminars in Immunopathology
Seminars in Immunopathology 医学-病理学
CiteScore
19.80
自引率
2.20%
发文量
69
审稿时长
12 months
期刊介绍: The aim of Seminars in Immunopathology is to bring clinicians and pathologists up-to-date on developments in the field of immunopathology.For this purpose topical issues will be organized usually with the help of a guest editor.Recent developments are summarized in review articles by authors who have personally contributed to the specific topic.
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