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cytokine release syndrome

肿瘤

关键词肿瘤 疾病 细胞因子风暴

词汇介绍

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解析

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。

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

CD3 bispecific antibody–induced cytokine release is dispensable for cytotoxic T cell activity复制标题

CD3双特异性抗体诱导的细胞因子释放对于细胞毒性T细胞活性是可有可无的

发表时间:2019-09-04

影响因子:17.2

作者: Teemu T. Junttila

期刊:Sci Transl Med

T cell-retargeting therapies have transformed the therapeutic landscape of oncology. Regardless of the modality, T cell activating therapies are commonly accompanied by systemic cytokine release, which can progress to deadly cytokine release syndrome (CRS). Because of incomplete mechanistic understanding of the relationship between T cell activation and systemic cytokine release, optimal toxicity management that retains full therapeutic potential remains unclear. Here, we report the cell type-specific cellular mechanisms that link CD3 bispecific antibody-mediated killing to toxic cytokine release. The immunologic cascade is initiated by T cell triggering, whereas monocytes and macrophages are the primary source of systemic toxic cytokine release. We demonstrate that T cell-generated tumor necrosis factor-α (TNF-α) is the primary mechanism mediating monocyte activation and systemic cytokine release after CD3 bispecific treatment. Prevention of TNF-α release is sufficient to impair systemic release of monocyte cytokines without affecting antitumor efficacy. Systemic cytokine release is only observed upon initial exposure to CD3 bispecific antibody not subsequent doses, indicating a biological distinction between doses. Despite impaired cytokine release after second exposure, T cell cytotoxicity remained unaffected, demonstrating that cytolytic activity of T cells can be achieved in the absence of cytokine release.

译文

T细胞靶向疗法已经改变了肿瘤学的治疗方式。无论采用哪种方式,T细胞活化疗法通常都会伴随全身性细胞因子释放,这可能会发展为致命的细胞因子释放综合征(CRS)。由于对T细胞活化和系统性细胞因子释放之间的关系的不完整的机械理解,尚不清楚保留全部治疗潜力的最佳毒性管理。在这里,我们报告了将CD3双特异性抗体介导的杀伤与有毒细胞因子释放联系起来的特定细胞类型的细胞机制。免疫级联反应是由T细胞触发引发的,而单核细胞和巨噬细胞是全身毒性细胞因子释放的主要来源。我们证明T细胞生成的肿瘤坏死因子-α(TNF-α)是介导CD3双特异性治疗后介导单核细胞激活和系统性细胞因子释放的主要机制。预防TNF-α释放足以削弱单核细胞细胞因子的全身释放,而不会影响抗肿瘤功效。仅在最初暴露于CD3双特异性抗体时才观察到全身性细胞因子释放,而在后续剂量中则观察不到,表明剂量之间存在生物学差异。尽管第二次暴露后细胞因子释放受损,但T细胞的细胞毒性仍然不受影响,这表明在不释放细胞因子的情况下可以实现T细胞的溶细胞活性。