Pal Sumanta K, Hu Adriana, Chang Mark, Figlin Robert A
City of Hope Comprehensive Cancer Center, Duarte, California.
Cedars-Sinai Medical Center, Los Angeles, California.
Clin Adv Hematol Oncol. 2014 Feb;12(2):90-9.
The treatment of metastatic renal cell carcinoma (mRCC) has evolved markedly over the past decade, broaden- ing beyond immune-based strategies (eg, interleukin-2 and interferon-α) to include targeted agents (eg, sunitinib [Sutent, Pfizer] and sorafenib [Nexavar, Bayer]). Recently, there has been a renewed interest in immune-based strategies, with clinical trials underway to assess vaccines and other immunomodulatory agents. Of particular interest are agents that inhibit the interaction between the programmed death-1 (PD-1) receptor and its ligand (PD-L1) at the T-cell/antigen-presenting cell interface. This interaction produces T-cell anergy and therefore stifles the antitumor immune response. Monoclonal antibodies to PD-1 (eg, nivolumab, lambrolizumab, and pidilizumab) and PD-L1 (MPDL3280A and BMS-936559) are in various stages of clinical development. The clinical trajectory of these agents is discussed herein, with specific attention to the potential placement of PD-1/ PD-L1 inhibition in the crowded therapeutic landscape of mRCC.
在过去十年中，转移性肾细胞癌（mRCC）的治疗方法有了显著进展，从基于免疫的策略（如白细胞介素-2和干扰素-α）扩展到包括靶向药物（如舒尼替尼[Sutent，辉瑞公司]和索拉非尼[Nexavar，拜耳公司]）。最近，人们对基于免疫的策略重新产生了兴趣，正在进行临床试验以评估疫苗和其他免疫调节药物。特别令人感兴趣的是在T细胞/抗原呈递细胞界面抑制程序性死亡-1（PD-1）受体与其配体（PD-L1）之间相互作用的药物。这种相互作用会导致T细胞无反应性，从而抑制抗肿瘤免疫反应。针对PD-1（如纳武单抗、兰布单抗和匹地利珠单抗）和PD-L1（MPDL3280A和BMS-936559）的单克隆抗体正处于不同的临床开发阶段。本文讨论了这些药物的临床进展，特别关注在mRCC拥挤的治疗格局中PD-1/PD-L1抑制的潜在地位。
