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嵌合抗原受体 T 细胞治疗相关毒性的内皮细胞关键作用及干预策略。

The critical role of endothelial cell in the toxicity associated with chimeric antigen receptor T cell therapy and intervention strategies.

机构信息

Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.

出版信息

Ann Hematol. 2024 Jul;103(7):2197-2206. doi: 10.1007/s00277-024-05640-z. Epub 2024 Feb 8.

Abstract

Chimeric antigen receptor (CAR)-T cell therapy has shown promising results in patients with hematological malignancies. However, many patients still have poor prognoses or even fatal outcomes due to the life-threatening toxicities associated with the therapy. Moreover, even after improving the known influencing factors (such as number or type of CAR-T infusion) related to CAR-T cell infusion, the results remain unsatisfactory. In recent years, it has been found that endothelial cells (ECs), which are key components of the organization, play a crucial role in various aspects of immune system activation and inflammatory response. The levels of typical markers of endothelial activation positively correlated with the severity of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxic syndrome (ICANS), suggesting that ECs are important targets for intervention and toxicity prevention. This review focuses on the critical role of ECs in CRS and ICANS and the intervention strategies adopted.

摘要

嵌合抗原受体 (CAR)-T 细胞疗法在血液系统恶性肿瘤患者中显示出良好的效果。然而,由于该疗法相关的危及生命的毒性,许多患者的预后仍然较差,甚至导致死亡。此外,即使改善了与 CAR-T 细胞输注相关的已知影响因素(如 CAR-T 输注的数量或类型),结果仍然不尽如人意。近年来,人们发现内皮细胞(ECs)作为组织的关键组成部分,在免疫系统激活和炎症反应的各个方面发挥着至关重要的作用。内皮细胞激活的典型标志物水平与细胞因子释放综合征(CRS)和免疫效应细胞相关神经毒性综合征(ICANS)的严重程度呈正相关,表明 ECs 是干预和毒性预防的重要靶点。这篇综述重点关注了 ECs 在 CRS 和 ICANS 中的关键作用,以及所采用的干预策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b42/11224091/28cdceefc012/277_2024_5640_Fig1_HTML.jpg

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