[摘 要] 目的：探索性临床试验初步观察PD-1抑制剂联合脐血NK细胞治疗晚期恶性实体瘤的安全性与疗效。方法：研究 对象为2019年12月至2021年12月西安医学院第二附属医院收治的3例晚期实体瘤患者，依据肿瘤类型、参照CSCO指南，采用 标准化疗、靶向治疗或贝伐珠单抗联合PD-1抑制剂进行21 d为一疗程的多疗程治疗，期间适时进行脐血NK细胞输注治疗 （8 × 107个/次）。每个治疗周期均检测患者靶病灶大小、肿瘤标志物水平、外周血中12种细胞因子水平及淋巴细胞亚群情况，同 时评估患者不良反应发生情况。结果：3例患者经PD-1抑制剂联合脐血NK细胞治疗后，2例患者达到疾病稳定（SD；依照 RECIST 1.1），其中1例患者持续118 d，另1例患者持续92 d。在NK细胞输注治疗后，患者1肿瘤标志物CA199显著下降到正常 值范围内并维持3个随访期，患者2肿瘤标志物CA199、CA242和CA724均出现显著下降。结论：NK细胞与化疗和PD-1抑制剂 联合治疗实体瘤具有一定的疗效，本研究中3例患者未出现严重免疫相关不良反应。

[Abstract] Objective: To preliminarily investigate the safety and efficacy of programmed death-1 (PD-1) inhibitor combined with cord blood-derived natural killer cells (NK cells) in the treatment of advanced malignant solid tumors in an exploratory clinical trial. Methods: Three patients with advanced solid tumors treated at the Second Affiliated Hospital of Xi 'an Medical University from December 2019 to December 2021 were enrolled. According to tumor type and CSCO guidelines, patients received multiple treatment cycles (21 days per cycle) consisting of standard chemotherapy, targeted therapy, or bevacizumab combined with PD-1 inhibitor. Umbilical cord blood-derived NK cells (8 × 107 cells per infusion) were infused at appropriate intervals during the treatment course. Target lesion size, tumor markers, levels of 12 peripheral blood cytokines, and lymphocyte subsets were assessed in each treatment cycle. Adverse events were also monitored throughout the treatment. Results: Following the treatment with PD-1 inhibitor combined with cord blood NK cells, 2 patients achieved stable disease (SD, per RECIST 1.1 criteria), with durations of 118 days and 92 days, respectively. After NK cell infusion, patient #1 exhibited a marked decrease in the tumor marker CA199 to normal range and sustained for three follow-up periods; patient #2 showed significant reductions in tumor markers CA199, CA242, and CA724. Conclusion: The combination of NK cells with chemotherapy and PD-1 inhibitor demonstrates potential therapeutic efficacy for solid tumors. No severe immune-related adverse reactions were observed in the three patients enrolled in this study.

陕西省教育厅一般专项科研项目（No. 21JK0881）；陕西省科学技术厅自然科学基础研究计划（No. 2022JQ-889）