抗 PD-1 单克隆抗体 REGN2810 对转移性基底细胞癌和皮肤鳞状细胞癌的疗效。
Responses of metastatic basal cell and cutaneous squamous cell carcinomas to anti-PD1 monoclonal antibody REGN2810.
机构信息
Sarah Cannon Research Institute at HealthONE, Denver, CO USA.
Department of Medicine, Providence Portland Medical Center, Portland, OR USA.
出版信息
J Immunother Cancer. 2016 Nov 15;4:70. doi: 10.1186/s40425-016-0176-3. eCollection 2016.
BACKGROUND
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.
CASE PRESENTATIONS
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).
CONCLUSIONS
These case reports suggest that UV-associated skin cancers, beyond melanoma, are sensitive to PD-1 blockade.
TRIAL REGISTRATION
Clinicaltrials.gov NCT02383212. Registered 2 February 2015.
背景
基底细胞癌（BCC）和皮肤鳞状细胞癌（CSCC）都有暴露于紫外线的风险因素，因此这些肿瘤具有较高的突变负担。在其他恶性肿瘤中，高突变负担与针对程序性死亡 1（PD-1）免疫检查点受体的抗体治疗的临床获益相关。高度突变的肿瘤更可能表达免疫原性的肿瘤新抗原，吸引效应 T 细胞，而 PD-1 免疫检查点的阻断可以释放这些效应 T 细胞。
病例介绍
本报告描述了一名转移性 BCC 患者和一名转移性 CSCC 患者，他们在一项正在进行的 1 期试验（NCT02383212）中接受了 REGN2810（一种全人源抗 PD-1 单克隆抗体）的治疗。CSCC 患者经历了持续的完全缓解（16 个月以上），BCC 患者经历了持续的部分缓解（12 个月以上）。
结论
这些病例报告表明，除黑色素瘤外，与紫外线相关的皮肤癌对 PD-1 阻断敏感。
试验注册
Clinicaltrials.gov NCT02383212。注册于 2015 年 2 月 2 日。
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