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非小细胞肺癌免疫治疗的当前观点

Current Perspectives in Immunotherapy for Non-Small Cell Lung Cancer.

作者信息

Garon Edward B

机构信息

Director of Thoracic Oncology Program, Jonsson Comprehensive Cancer Center, University of California-Los Angeles, Los Angeles, CA.

出版信息

Semin Oncol. 2015 Oct;42 Suppl 2:S11-8. doi: 10.1053/j.seminoncol.2015.09.019. Epub 2015 Sep 11.

Abstract

In non-small cell lung cancer (NSCLC), the first immune checkpoint inhibitor to be approved by the US Food and Drug Administration was nivolumab, based on a survival advantage over docetaxel in recurrent squamous NSCLC, a difficult-to-treat histology. In addition, several other immune checkpoint inhibitors are also in late-stage development. Most of these agents inhibit the programmed cell death protein 1 (PD-1) pathway, targeting either the PD-1 receptor or its ligand, programmed cell death ligand 1 (PD-L1). In addition to nivolumab, pembrolizumab is a PD-1 inhibitor under investigation in NSCLC, and atezolizumab (MPDL3280A), durvalumab (MEDI4736), and avelumab (MSB0010718C) are PD-L1 inhibitors under investigation. The cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) immune checkpoint inhibitors ipilimumab and tremelimumab are also under investigation in NSCLC, largely as part of combination approaches rather than as monotherapy. PD-L1 expression as a potential biomarker to select patients most likely to respond to inhibitors of the PD-1 pathway has been widely studied.

摘要

在非小细胞肺癌(NSCLC)中,美国食品药品监督管理局批准的首个免疫检查点抑制剂是纳武单抗,这是基于其在复发鳞状NSCLC(一种难以治疗的组织学类型)中相对于多西他赛具有生存优势。此外,其他几种免疫检查点抑制剂也正处于后期研发阶段。这些药物大多抑制程序性细胞死亡蛋白1(PD-1)通路,靶向PD-1受体或其配体程序性细胞死亡配体1(PD-L1)。除纳武单抗外,派姆单抗是一种正在NSCLC中进行研究的PD-1抑制剂,阿特珠单抗(MPDL3280A)、度伐鲁单抗(MEDI4736)和阿维鲁单抗(MSB0010718C)是正在进行研究的PD-L1抑制剂。细胞毒性T淋巴细胞相关抗原4(CTLA-4)免疫检查点抑制剂伊匹单抗和曲美木单抗也正在NSCLC中进行研究,主要作为联合治疗方案的一部分,而非单一疗法。PD-L1表达作为选择最有可能对PD-1通路抑制剂产生反应的患者的潜在生物标志物已得到广泛研究。

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