Redman Jason M, Gibney Geoffrey T, Atkins Michael B
Georgetown Lombardi Comprehensive Cancer Center 3970 Reservoir Road, NW Research Building, Room E501, 20007, Washington DC, USA.
Department of Medicine, Georgetown University Medical Center, Washington DC, USA.
BMC Med. 2016 Feb 6;14:20. doi: 10.1186/s12916-016-0571-0.
In recent years, the introduction and Federal Drug Administration approval of immune checkpoint inhibitor antibodies has dramatically improved the clinical outcomes for patients with advanced melanoma. These antagonist monoclonal antibodies are capable of unleashing dormant or exhausted antitumor immunity, which has led to durable complete and partial responses in a large number of patients. Ipilimumab targets the cytotoxic T lymphocyte-associated protein 4 (CTLA-4) receptor. Nivolumab and pembrolizumab target programmed cell death protein 1 (PD-1) receptors and have proven to be superior to ipilimumab alone. The combination of ipilimumab and nivolumab has yielded higher response rates, greater tumor shrinkage, and longer progression-free survival than either monotherapy alone. As other promising immunotherapies for melanoma proceed through clinical trials, future goals include defining the role of immune checkpoint inhibitors as adjuvant therapy, identifying optimal combination strategies, and developing reliable predictive biomarkers to guide treatment selection for individual patients.
近年来，免疫检查点抑制剂抗体的引入及美国食品药品监督管理局（FDA）的批准显著改善了晚期黑色素瘤患者的临床预后。这些拮抗性单克隆抗体能够释放休眠或耗竭的抗肿瘤免疫力，从而使大量患者产生持久的完全缓解和部分缓解。伊匹单抗靶向细胞毒性T淋巴细胞相关蛋白4（CTLA-4）受体。纳武单抗和派姆单抗靶向程序性细胞死亡蛋白1（PD-1）受体，且已被证明优于单独使用伊匹单抗。与单药治疗相比，伊匹单抗和纳武单抗联合使用产生了更高的缓解率、更大程度上的肿瘤缩小以及更长的无进展生存期。随着其他有前景的黑色素瘤免疫疗法进入临床试验阶段，未来的目标包括明确免疫检查点抑制剂作为辅助治疗的作用、确定最佳联合策略以及开发可靠的预测生物标志物以指导个体患者的治疗选择。
