Toxicity and management in CAR T-cell therapy.

Toxicity and management in CAR T-cell therapy.
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DOI:
10.1038/mto.2016.11
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发表时间:
2016
期刊:
Molecular therapy oncolytics
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其他
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T细胞可以通过嵌合抗原受体(CAR)的表达进行基因修饰以靶向肿瘤。最值得注意的是,CAR - T细胞已经证明了在血液系统恶性肿瘤中的临床疗效,当靶向实体肿瘤时反应更温和。然而,CAR - T细胞也具有引发预期和意外毒性的能力,包括:细胞因子释放综合征、神经毒性、“靶/off肿瘤”识别和过敏反应。理论上的毒性包括继发于插入性肿瘤的克隆扩增、移植物抗宿主病和脱靶抗原识别尚未得到临床证实。消除毒性已成为这一新兴技术成功应用的关键一步。为此,我们回顾了CAR - T细胞的报道和理论上的毒性及其管理。
T cells can be genetically modified to target tumors through the expression of a chimeric antigen receptor (CAR). Most notably, CAR T cells have demonstrated clinical efficacy in hematologic malignancies with more modest responses when targeting solid tumors. However, CAR T cells also have the capacity to elicit expected and unexpected toxicities including: cytokine release syndrome, neurologic toxicity, “on target/off tumor” recognition, and anaphylaxis. Theoretical toxicities including clonal expansion secondary to insertional oncogenesis, graft versus host disease, and off-target antigen recognition have not been clinically evident. Abrogating toxicity has become a critical step in the successful application of this emerging technology. To this end, we review the reported and theoretical toxicities of CAR T cells and their management.
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