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一个前沿技术的起点:使用T细胞免疫治疗淋巴瘤

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发表于 2015-12-9 00:06:15 | 显示全部楼层 |阅读模式
Beginning of a novel frontier: T-cell directed immune  manipulation in lymphomas.
Abstract
Checkpoint inhibitors with monoclonal antibodies targeting the CTLA-4 or PD-1 axis have revolutionized treatment in some solid tumours, especially melanoma and lung. The role of the CTLA-4 and PD-1 pathways and their inhibition in lymphoma may be different compared to solid tumours. In heavily pre-treated Hodgkin lymphoma, PD-1 directed treatment has led to high remission rates. Several studies are now conducted also including diffuse large B-cell and follicular lymphoma. Beside antibody-based immunotherapy, treatment with chimeric antigen receptor (CAR) T-cells has also come back to the focus of recent studies. Clinical evidence of CAR T-cell treatment in B-cell malignancies is limited to small series, because of the dedicated resources needed. However, impressive response rates have been observed, but toxicities associated with cytokine release can be very severe and fatal. We herein review background, early clinical evidence and future perspectives of T-cell directed immune manipulation for lymphomas including checkpoint inhibitors and CAR T-cell therapies.
KEYWORDS:
Anti PD-1 treatment; CAR; Chimeric antibody receptor; Immunotherapy; Ipilimumab; Lymphoma; Nivolumab; Pembrolizumab; Pidilizumab; Review; T-cells
一个前沿技术的起点:使用T细胞免疫治疗淋巴瘤
摘要:
检查点抑制剂和单克隆抗体靶向CTLA-4PD-1 在一些实体肿瘤的治疗中已经起到了革命性的作用,尤其是针对黑色素瘤和肺癌。CTLA-4PD-1途径所扮演的角色及其在淋巴瘤中起的抑制作用与实体瘤是不同的。在严重预处理的霍奇金淋巴瘤患者中,PD-1介导的治疗已经能够有较高的缓解率。目前还进行了一些其他研究,包括治疗弥漫性大B细胞和滤泡性淋巴瘤。除了以抗体为基础的免疫治疗,使用嵌合抗原受体修饰的T细胞治疗已经又回归到最近研究的核心。CAR-T细胞治疗B细胞淋巴瘤的一些临床证据是有限的,因为所需资源的限制。然而,CAR-T细胞治疗能够观察到令人激动的效果,虽然与细胞因子释放相关的毒性可能会比较严重。我们在这里回顾了使用T细胞靶向免疫治疗淋巴瘤,包括免疫检查点抑制和CAR-T细胞治疗的背景、早期临床证据以及未来治疗的观点。

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Beginning of a novel frontier T-cell directed 2015.12.8.pdf

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