摘要

Genetically modified T cells that express a chimeric antigen receptor (CAR) are opening a new frontier in cancer immunotherapy. CAR T cells currently are in clinical trials for many cancer types. Cytokine release syndrome (CRS) and neurotoxicities (CAR-related encephalopathy syndrome, CRES) are major adverse events limiting wide deployment of the CAR T cell treatment. Major efforts are ongoing to characterize the pathogenesis and etiology of CRS and CRES. Mouse models have been established to facilitate the study of pathogenesis of the major toxicities of CAR T cells. Myeloid cells including macrophages and monocytes, not the CAR T cells, were found to be the major cells mediating CRS and CRES by releasing IL-1 and IL-6 among other cytokines. Blocking IL-1 or depletion of monocytes abolished both CRS and CRES, whereas IL-6 blocker can ameliorate CRS but not CRES. Therefore, both IL-1 and IL-6 are major cytokines for CRS, though IL-1 is responsible for CRES. It was also demonstrated in the mouse models that blocking CRS does not interfere with the CAR T cell antitumor functions. We summarized new developments in the grading, modeling, and possible new therapeutic approaches for CRS and CRES in this review.

译文

表达嵌合抗原受体 (CAR) 的转基因 T 细胞正在开辟癌症免疫治疗的新领域。CAR T 细胞目前正在对许多癌症类型进行临床试验。细胞因子释放综合征 (CRS) 和神经毒性 (CAR 相关脑病综合征,CRES) 是限制 CAR T 细胞治疗广泛应用的主要不良事件。目前正在努力描述 CRS 和 CRES 的发病机制和病因。已经建立了小鼠模型,以促进 CAR T 细胞主要毒性的发病机制研究。骨髓细胞包括巨噬细胞和单核细胞,而不是 CAR T 细胞,被发现是通过释放 IL-1 和其他细胞因子中的 IL-6 来介导 CRS 和 CRES 的主要细胞。阻断单核细胞的 IL-1 或耗竭可以消除 CRS 和 CRES,而 IL-6 阻滞剂可以改善 CRS 而不是 CRES。因此,IL-1 和 IL-6 都是 CRS 的主要细胞因子,尽管 IL-1 负责 CRES。在小鼠模型中也证明,阻断 CRS 不会干扰 CAR T 细胞的抗肿瘤功能。我们在这篇综述中总结了 CRS 和 CRES 分级、建模和可能的新治疗方法的新发展。

cytokine release syndrome

肿瘤 细胞因子风暴 疾病
概述  :  

细胞因子释放综合征(CRS),也称“细胞因子风暴”,是指淋巴细胞在应用单克隆抗体、细胞因子等治疗或感染后出现活化、溶解,并释放出大量细胞因子所导致的一组临床综合征。具体地说,单克隆抗体等药物在体内与靶细胞相关抗原结合后,产生活化并释放趋化因子富集单核细胞、巨噬细胞、细胞毒T细胞和自然杀伤细胞至结合区域,发生免疫反应,继发靶细胞破坏或凋亡,靶细胞和免疫效应细胞内的细胞因子释放入血,达到一定数量并产生相应效应,出现的一系列临床特异性表现,称为CRS。CRS是CAR-T治疗时较为常见的急性不良反应

Cytokine   英 /'saɪtə(ʊ)kaɪn/   美 /'saɪtə,kaɪn/

释    义   n. [细胞] 细胞因子;细胞激素

例    句   Such a novel type of controlled release system may have potential to be applied for controlled cytokine delivery and the cartilage tissue engineering. 这种新型药物控制释放系统在细胞因子的控制释放及软骨组织工程中有潜在的应用价值。

 

Release   英 /rɪ'liːs/   美 /rɪ'lis/

释    义   v. 释放;放开;发泄;免除;松开;使不紧张;公开;解禁;放弃(权利);n. 释放;发布;新发行的东西;排放;解脱;新闻稿;让予;宣泄;释放装置

同根词   releasing n. 释放;松释动作;脱扣释放;releasing v. 释放;排放(release的现在分词)

例    句   Sex stimulates the release of vasopressin and oxytocin in people, as well as voles, though the role of these hormones in the human brain is not yet well understood.  虽然抗利尿激素和催产素在人脑内的角色仍未被透彻了解,但与田鼠一样,人体在受到性刺激时也会释放这些荷尔蒙。

 

Syndrome   英 /'sɪndrəʊm/   美 /'sɪndrəm/

释    义   n. [临床] 综合症状;并发症状;校验子;并发位

例    句   The researchers found that some of the people with this syndrome lack a gene for BDNF and have correspondingly low blood levels of the substance. 研究人员发现患有这种综合症的一些人缺少表达BDNF的基因,并且血液中这种物质的水平相对较低。

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