黑色素瘤治疗新组合--Nivolumab和Ipilimumab

New combination of melanoma treatment:Nivolumab and ipilimumab

Nivolumab(商品名Opdivo),一种由百时美施贵宝公司研制的单克隆抗体,是程序性死亡受体(PD-1)阻断剂。至2015年10月,FDA已批准其单用或联用ipilimumab(商品名Yervoy)用于黑色素瘤的治疗。Nivolumab作为目前最受关注的新一类抗肿瘤药物,可治疗多种类型的肿瘤,能够实质性提高客观响应率,其通过结合PD-1并阻断肿瘤细胞内部PD-1通路对T细胞的抑制作用,同时联用ipilimumab抑制CTLA-4对T细胞的负调控作用,共同增强活化T细胞,攻击肿瘤,这种治疗手段是免疫治疗的研究热点。笔者就nivolumab及ipilimumab的研发历程、基本性质、作用机制、药动学、药效学、临床试验及不良反应等信息作一概述,希望能对医院临床用药提供帮助和指导。

Nivolumab （brand name Opdivo） is a monoclonal antibody that can blockthe programmed death receptor-1 （PD.-1）, developed by Bristol-Myers Squibb company（BMS）. From October 2015, the FDA has approvednivolumab as a treatment indication for unresectable or metastatic melanoma in combination with ipilimumab （brand name Yervoy） or as a single agent. As a new interesting class of anticancer agents, the efficacy of nivolumabwasevaluated in several kinds of tumors. Through the binding PD-1 and blocking the inhibition of PD-1 pathwayto T cellswithintumor cells, Nivolumabcombined with ipilimumab inhibit CTLA-4 on negative regulatory roleofT cells, increase the activation of T cells, and attack the tumors. The treatment is a hot topic in the research of immunotherapy.This article reviewed the development process, mechanism, pharmacokinetics, pharmacodynamics, clinical trials, adverse reactions and domestic R ＆ D trends of nivolumab and ipilimumab.