Guangdong Provincial Key Laboratory of Proteomics, State Key Laboratory of Organ Failure Research, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
Biological Treatment Center, Fuda Cancer Hospital, Jinan University, Guangzhou, China.
J Clin Invest. 2020 May 1;130(5):2560-2569. doi: 10.1172/JCI132712.
BACKGROUNDThe anti-programmed cell death 1 (anti-PD-1) antibody pembrolizumab is clinically active against non-small cell lung cancer (NSCLC). In addition to T cells, human natural killer (NK) cells, reported to have the potential to prolong the survival of patients with advanced NSCLC, also express PD-1. This study aimed to investigate the safety and efficacy of pembrolizumab plus allogeneic NK cells in patients with previously treated advanced NSCLC.METHODSIn total, 109 enrolled patients with a programmed death ligand 1 (PD-L1) tumor proportion score (TPS) of 1% or higher were randomly allocated to group A (n = 55 patients given pembrolizumab plus NK cells) or group B (n = 54 patients given pembrolizumab alone). The patients received i.v. pembrolizumab (10 mg/kg) once every 3 weeks and continued treatment until the occurrence of tumor progression or unacceptable toxicity. The patients in group A continuously received 2 cycles of NK cell therapy as 1 course of treatment.RESULTSIn our study, patients in group A had longer survival than did patients in group B (median overall survival [OS]: 15.5 months vs. 13.3 months; median progression-free survival [PFS]: 6.5 months vs. 4.3 months; P < 0.05). In group A patients with a TPS of 50% or higher, the median OS and PFS was significantly longer. Moreover, the patients in group A treated with multiple courses of NK cell infusion had better OS (18.5 months) than did those who received a single course of NK cell infusion (13.5 months).CONCLUSIONPembrolizumab plus NK cell therapy yielded improved survival benefits in patients with previously treated PD-L1+ advanced NSCLC.TRIAL REGISTRATIONClinicalTrials.gov NCT02843204.FUNDINGThis work was supported by grants from the National Natural Science Foundation of China (NSFC) - Guangdong Joint Foundation of China (no. U1601225); the NSFC (no. 81671965); the Guangdong Provincial Key Laboratory Construction Project of China (no. 2017B030314034); and the Key Scientific and Technological Program of Guangzhou City (no. 201607020016).
抗程序性死亡 1（抗 PD-1）抗体 pembrolizumab 对非小细胞肺癌（NSCLC）具有临床活性。除 T 细胞外，据报道，具有延长晚期 NSCLC 患者生存潜力的人类自然杀伤（NK）细胞也表达 PD-1。本研究旨在探讨先前治疗的晚期 NSCLC 患者中 pembrolizumab 联合异体 NK 细胞的安全性和疗效。
共纳入 109 名程序性死亡配体 1（PD-L1）肿瘤比例评分（TPS）为 1%或更高的患者，随机分为 A 组（n = 55 例患者接受 pembrolizumab 联合 NK 细胞治疗）或 B 组（n = 54 例患者接受 pembrolizumab 单药治疗）。患者静脉注射 pembrolizumab（10 mg/kg），每 3 周 1 次，持续治疗直至肿瘤进展或不可接受的毒性发生。A 组患者连续接受 2 个周期的 NK 细胞治疗作为 1 个疗程。
在本研究中，A 组患者的总生存期（OS）长于 B 组（中位 OS：15.5 个月比 13.3 个月；中位无进展生存期（PFS）：6.5 个月比 4.3 个月；P < 0.05）。A 组 TPS 为 50%或更高的患者，中位 OS 和 PFS 明显延长。此外，接受多次 NK 细胞输注治疗的 A 组患者的 OS 更好（18.5 个月），而接受单次 NK 细胞输注的患者的 OS 较差（13.5 个月）。
pembrolizumab 联合 NK 细胞治疗可改善先前治疗的 PD-L1+晚期 NSCLC 患者的生存获益。
ClinicalTrials.gov NCT02843204。
本工作得到中国国家自然科学基金-广东联合基金（U1601225）；中国国家自然科学基金（81671965）；广东省重点实验室建设项目（2017B030314034）；以及广州市重点科技计划（201607020016）的支持。
