Responses of metastatic basal cell and cutaneous squamous cell carcinomas to anti-PD1 monoclonal antibody REGN2810.

Responses of metastatic basal cell and cutaneous squamous cell carcinomas to anti-PD1 monoclonal antibody REGN2810.
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转移性基底细胞和皮肤鳞状细胞癌对抗PD1单克隆抗体regn2810的反应。

DOI:
10.1186/s40425-016-0176-3
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发表时间:
2016
影响因子:
10.9
通讯作者:
Fury MG
Fury MG
中科院分区:
医学2区
文献类型:
--
作者:
Falchook GS;Leidner R;Stankevich E;Piening B;Bifulco C;Lowy I;Fury MG

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基底细胞癌(BCC)和皮肤鳞状细胞癌(CSCC)共同暴露于紫外线作为主要的风险因素,因此这些肿瘤具有高突变负荷。在其他恶性肿瘤中,高突变负荷与使用针对程序性死亡1(PD-1)免疫检查点受体的抗体治疗的临床获益相关。高度突变的肿瘤更有可能表达免疫原性肿瘤新抗原,这些抗原吸引效应T细胞,这些效应T细胞可以通过阻断PD-1免疫检查点而释放。本报告描述了1例转移性BCC患者和1例转移性CSCC患者,他们在一项正在进行的I期试验(NCT 02383212)中接受了REGN 2810(一种全人源抗PD-1单克隆抗体)治疗。CSCC患者经历了持续的完全缓解(16+个月),BCC患者经历了持续的部分缓解(12+个月)。这些病例报告表明,除黑色素瘤外,紫外线相关的皮肤癌对PD-1阻断剂敏感。Clinicaltrials.gov 2015年2月2日注册。
Basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (CSCC) share exposure to UV light as the dominant risk factor, and these tumors therefore harbor high mutation burdens. In other malignancies, high mutation burden has been associated with clinical benefit from therapy with antibodies directed against the Programmed Death 1 (PD-1) immune checkpoint receptor. Highly mutated tumors are more likely to express immunogenic tumor neoantigens that attract effector T cells, which can be unleashed by blockade of the PD-1 immune checkpoint. This report describes a patient with metastatic BCC and a patient with metastatic CSCC who were treated with REGN2810, a fully human anti-PD-1 monoclonal antibody, in an ongoing phase 1 trial (NCT02383212). The CSCC patient has experienced an ongoing complete response (16+ months), and the BCC patient has experienced an ongoing partial response (12+ months). These case reports suggest that UV-associated skin cancers, beyond melanoma, are sensitive to PD-1 blockade. Clinicaltrials.gov NCT02383212. Registered 2 February 2015.
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