【AI详解】Neurological updates: neurological complications of CAR-T therapy.

文献信息

一句话小结

嵌合抗原受体（CAR）T细胞治疗为难治性B细胞恶性肿瘤患者提供了新选择，但神经毒性（ICANS）是常见并发症，影响超过50%的患者。本文总结了CAR-T相关神经毒性的临床表现、机制及推荐治疗，以帮助神经科医生更好地理解和管理这种并发症，推动CAR-T疗法的临床应用。

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不良事件 · 嵌合抗原受体T细胞（CAR-T） · 神经系统 · 副作用

摘要

嵌合抗原受体（CAR）表达的T细胞现在为以往难治的B细胞恶性肿瘤患者提供了一种有效的治疗选择，并且正在开发用于广泛的其他肿瘤。然而，神经毒性是CAR-T细胞治疗的常见并发症，在某些患者群体中，超过50%的接受者会出现这种情况。自2018年以来，免疫效应细胞相关神经毒性综合征（ICANS）这一术语被用来描述和分级在CAR-T细胞及其他类似疗法后出现的神经毒性。CAR-T治疗后的ICANS通常是自限性的，但可能需要住院接受重症监护，且极少致死。随着CAR-T疗法进入常规临床实践，神经科医生了解神经并发症的性质变得尤为重要。在此，我们总结了CAR-T相关神经毒性的临床表现、机制、检查和推荐治疗，重点关注已获批准的CD19产品。

英文摘要

Chimeric antigen receptor (CAR)-expressing T cells now offer an effective treatment option for people with previously refractory B cell malignancies and are under development for a wide range of other tumours. However, neurological toxicity is a common complication of CAR-T cell therapy, seen in over 50% of recipients in some cohorts. Since 2018, the term immune effector cell-associated neurotoxicity syndrome (ICANS) has been used to describe and grade neurotoxicity seen after CAR-T cells and other similar therapies. ICANS following CAR-T therapy is usually self-limiting but can necessitate admission to the intensive care unit and is rarely fatal. As CAR-T therapies enter routine clinical practice, it is important for neurologists to be aware of the nature of neurological complications. Here, we summarise the clinical manifestations, mechanisms, investigations and recommended treatment of CAR-T-related neurotoxicity, focusing on the licensed CD19 products.

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主要研究问题

1. CAR-T疗法中ICANS的具体临床表现有哪些？
2. 目前有哪些机制被认为与CAR-T相关的神经毒性有关？
3. 针对CAR-T治疗后神经毒性的推荐治疗方案是什么？
4. 在临床实践中，如何有效监测和评估CAR-T治疗后的神经毒性？
5. 对于不同类型的肿瘤，CAR-T疗法引起的神经毒性是否存在差异？

核心洞察

研究背景和目的

嵌合抗原受体（CAR）T细胞疗法为难治性B细胞恶性肿瘤患者提供了一种有效的治疗选择，但其常见的神经毒性并未得到充分重视。文献旨在总结CAR-T疗法相关的神经毒性，包括其临床表现、机制、检查和推荐的治疗方案，特别是针对已获批准的CD19产品。

主要方法/材料/实验设计

本研究通过对现有文献的综述，重点关注CAR-T细胞治疗的神经毒性。研究设计为文献回顾，主要包括以下要素：

• 临床表现：分析CAR-T治疗后出现的各种神经毒性症状，如震颤、注意力和语言表达问题等。
• 机制：探讨神经毒性的潜在机制，包括细胞因子释放综合征（CRS）与神经毒性的关系。
• 调查方法：包括影像学检查（CT和MRI）、脑电图（EEG）和脑脊液分析等。
• 治疗策略：总结现有的治疗方案，特别是类固醇和其他支持性治疗。

关键结果和发现

1. 神经毒性表现：神经毒性表现多样，早期症状包括震颤、注意力缺陷和语言表达障碍。重症病例可表现为急性脑病、癫痫发作等。
2. 与CRS的关系：神经毒性通常在CRS症状出现后几天内发生，且严重神经毒性往往与先前的CRS相关。
3. 发病机制：研究发现细胞因子水平升高、血脑屏障破坏及CAR-T细胞的中枢神经系统渗透可能是神经毒性的主要机制。
4. 治疗效果：类固醇被证明对中重度神经毒性有效，但需谨慎使用以避免抑制CAR-T细胞的抗肿瘤效应。

主要结论/意义/创新性

CAR-T细胞疗法虽有效，但伴随的神经毒性需引起重视。了解神经毒性的表现及其机制对于优化治疗方案、提高患者的生活质量至关重要。该文献提供了对神经毒性的系统性评估，并提出了针对性管理建议，为临床医生提供了宝贵的参考。

研究局限性和未来方向

1. 局限性：目前对神经毒性的机制仍不完全清楚，且缺乏大规模临床试验数据支持。
2. 未来方向：未来的研究应集中在长期神经后果的评估、新型治疗策略的开发以及优化现有治疗方案的实施。探索不同CAR-T产品的神经毒性特征及其管理策略也将是重要的研究方向。

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引用本文的文献

1. Challenges and Prospects for Designer T and NK Cells in Glioblastoma Immunotherapy. - Victoria Smith Arnesen;Andrea Gras Navarro;Martha Chekenya - Cancers (2021)
2. [Mechanism and prevention strategies of neurotoxicity in CAR-T treatment of B cell tumors]. - Q Zhang;Y Xiao - Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi (2021)
3. Managing therapy-associated neurotoxicity in children with ALL. - Deepa Bhojwani;Ravi Bansal;Alan S Wayne - Hematology. American Society of Hematology. Education Program (2021)
4. In-Vivo Induced CAR-T Cell for the Potential Breakthrough to Overcome the Barriers of Current CAR-T Cell Therapy. - Tianqing Xin;Li Cheng;Chuchao Zhou;Yimeng Zhao;Zhenhua Hu;Xiaoyan Wu - Frontiers in oncology (2022)
5. Rehabilitation Needs for Patients Undergoing CAR T-Cell Therapy. - Obada Obaisi;Rhodora C Fontillas;Krina Patel;An Ngo-Huang - Current oncology reports (2022)
6. [Consensus of Chinese experts on the clinical management of chimeric antigen receptor T-cell-associated neurotoxicity (2022)]. - ; - Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi (2022)
7. Time to evolve: predicting engineered T cell-associated toxicity with next-generation models. - Emmanuel Donnadieu;Maik Luu;Miriam Alb;Brigitte Anliker;Silvia Arcangeli;Chiara Bonini;Biagio De Angelis;Rashmi Choudhary;David Espie;Anne Galy;Cam Holland;Zoltán Ivics;Chahrazade Kantari-Mimoun;Marie Jose Kersten;Ulrike Köhl;Chantal Kuhn;Bruno Laugel;Franco Locatelli;Ibtissam Marchiq;Janet Markman;Marta Angiola Moresco;Emma Morris;Helene Negre;Concetta Quintarelli;Michael Rade;Kristin Reiche;Matthias Renner;Eliana Ruggiero;Carmen Sanges;Hans Stauss;Maria Themeli;Jan Van den Brulle;Michael Hudecek;Monica Casucci - Journal for immunotherapy of cancer (2022)
8. Mechanisms of immune effector cell-associated neurotoxicity syndrome after CAR-T treatment. - Tianning Gu;Kejia Hu;Xiaohui Si;Yongxian Hu;He Huang - WIREs mechanisms of disease (2022)
9. Therapeutic targets and biomarkers of tumor immunotherapy: response versus non-response. - Dong-Rui Wang;Xian-Lin Wu;Ying-Li Sun - Signal transduction and targeted therapy (2022)
10. Metabolic Imaging in B-Cell Lymphomas during CAR-T Cell Therapy. - Flavia Linguanti;Elisabetta Maria Abenavoli;Valentina Berti;Egesta Lopci - Cancers (2022)

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