决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:Human epidermal growth factor receptor 2 (HER2)-specific chimeric antigen receptor (CAR) for tumor immunotherapy; recent progress.
由于人类表皮生长因子受体 2(HER2)在众多人类肿瘤中过表达或扩增且预后不良,近期研究聚焦于 HER2 靶向治疗。
由于人表皮生长因子受体2(HER2)在多种人类肿瘤中存在过表达或扩增且与不良预后相关,近期研究聚焦于HER2靶向治疗。HER2信号通路失调会促进肿瘤细胞持续生长和迁移,并刺激血管网络增殖,从而推动肿瘤血管生成和转移。大量研究明确显示,新兴HER2靶向疗法可能改善HER2阳性乳腺癌及胃癌/胃食管癌患者的结局。基于其强大的抗肿瘤潜力,表达HER2特异性嵌合抗原受体(CAR)的免疫细胞疗法近期受到越来越多关注。人T细胞和自然杀伤(NK)细胞可大量存在于肿瘤微环境中,主要参与肿瘤免疫监视,因此是表达人工构建CAR的理想基因工程改造候选细胞。本文介绍肿瘤细胞HER2信号的潜在靶点,以阐明HER2介导的肿瘤发生机制,并讨论近期关于HER2特异性CAR表达免疫细胞(CAR T和CAR NK细胞)治疗HER2表达肿瘤的研究发现。
Due to the overexpression or amplification of human epidermal growth factor receptor 2 (HER2) with poor prognosis in a myriad of human tumors, recent studies have focused on HER2-targeted therapies. Deregulation in HER2 signaling pathways is accompanied by sustained tumor cells growth concomitant with their migration and also tumor angiogenesis and metastasis by stimulation of proliferation of a network of blood vessels. A large number of studies have provided clear evidence that the emerging HER2-directed treatments could be the outcome of patients suffering from HER2 positive breast and also gastric/gastroesophageal cancers. Thanks to its great anti-tumor competence, immunotherapy using HER2-specific chimeric antigen receptor (CAR) expressing immune cell has recently attracted increasing attention. Human T cells and also natural killer (NK) cells can largely be found in the tumor microenvironment, mainly contributing to the tumor immune surveillance. Such properties make them perfect candidate for genetically modification to express constructed CARs. Herein, we will describe the potential targets of the HER2 signaling in tumor cells to clarify HER2-mediated tumorigenesis and also discuss recent findings respecting the HER2-specific CAR-expressing immune cells (CAR T and CAR NK cell) for the treatment of HER2-expressing tumors.
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