Seetharamu Nagashree, Budman Daniel R, Sullivan Kevin M
Monter Cancer Center, Northwell Health, Lake Success, NY 11042, USA.
Future Oncol. 2016 May;12(9):1151-63. doi: 10.2217/fon.16.20. Epub 2016 Mar 29.
Inhibitory ligands on tumor cells and their corresponding receptors on T cells are collectively called immune checkpoint molecules and have emerged as druggable targets that harness endogenous immunity to fight cancer. Immune checkpoint inhibitors targeting CTLA-4, PD-1 and PD-L1 have been developed for the treatment of patients with non-small-cell lung cancer and other malignancies, with impressive clinical activity, durable responses and a favorable toxicity profile. This article reviews the development, current status and future directions for some of these agents. The efficacy and safety data for drugs such as ipilimumab, nivolumab, pembrolizumab, atezolizumab and durvalumab are reviewed, along with combination strategies and response evaluation criteria. The toxicity profiles and predictive biomarkers of response are also discussed.
肿瘤细胞上的抑制性配体及其在T细胞上的相应受体统称为免疫检查点分子,已成为利用内源性免疫来对抗癌症的可药物化靶点。针对CTLA-4、PD-1和PD-L1的免疫检查点抑制剂已被开发用于治疗非小细胞肺癌和其他恶性肿瘤患者,具有令人印象深刻的临床活性、持久反应和良好的毒性特征。本文综述了其中一些药物的研发、现状和未来方向。还综述了伊匹木单抗、纳武单抗、帕博利珠单抗、阿特珠单抗和度伐利尤单抗等药物的疗效和安全性数据,以及联合策略和反应评估标准。还讨论了毒性特征和反应预测生物标志物。