肝脏 ›› 2020, Vol. 25 ›› Issue (10): 1055-1057.

• 肝癌 • 上一篇    下一篇

NK细胞治疗肝脏恶性肿瘤疗效评价的安全性及有效性

李莉, 周丰, 王晓今, 徐以兵, 施莉琴, 李震宇, 周桁, 傅青春, 陈成伟   

  1. 上海市公共卫生临床中心肝病中心(李莉,傅青春); 中国人民解放军海军第九〇五医院肝病中心 (李莉,周丰,王晓今,施莉琴,李震宇,周桁,陈成伟); 上海宇研生物技术有限公司(徐以兵)
  • 收稿日期:2020-07-22 出版日期:2020-10-31 发布日期:2020-12-18
  • 通讯作者: 傅青春,Email: qcfu85@163.com;陈成伟,Email: ccw2@163.com
  • 基金资助:
    长宁区卫生健康委员会科研项目(20154Y017)

A clinical study on the efficacy of natural killer cell therapy on patients with malignant liver tumors

LI Li1,2, ZHOU Feng1, WANG Xiao-jin1, XU Yi-bing3, SHI Li-qin1, LI Zhen-yu1, ZHOU Heng1, FU Qing-chun1,2, CHEN Cheng-wei1   

  1. 1. 905 Hospital, Liver Disease Center;
    2. Shanghai Clinical Center of Public Health, Center of Liver Disease;
    3. Shanghai Yuyan Biotechnology Co., LTD
  • Received:2020-07-22 Online:2020-10-31 Published:2020-12-18
  • Contact: FU Qing-chun,Email qcfu85@163.com;CHEN Cheng-wei,Email ccw2@163.com

摘要: 目的 观察NK细胞过继回输治疗肝脏恶性肿瘤的安全性及有效性。方法 选择10例经手术切除、肝动脉介入、微波消融或放化疗后的肝恶性肿瘤患者,回输其直系亲属来源体外培养的NK细胞。通过观察患者异体NK细胞过回输后反应、比较治疗前后生活质量(KPS评分)、肝肾功能、血常规、循环肿瘤细胞(CTC)、有效缓解率、总体生存率等指标变化,评价该治疗方法的安全性和近期疗效。结果 异体NK细胞回输后,1例患者细胞输注后半小时出现畏寒、寒战、胸闷,给予对症处理,15 min后症状缓解体温升高,最高至39.9℃,伴恶心、呕吐,予以胃复安及泰诺处理后,症状逐渐消失,次日有轻度肌肉酸痛;1例出现失眠;5例患者的精神、食欲、体力明显好转。10例患者输注后24 h CTC数由3~5/mL降至1~3/mL,差异有统计学意义(P<0.05),肝、肾功能均无明显变化。随访3~36个月,根据实体瘤疗效评价标准,患者3个月总体生存率100%,有效缓解率80%(无死亡,2例SD,3例PR,5例CR),6个月总体生存率90%,有效缓解率80%(1例死亡,1例PD,3例PR,5例病CR); 12个月总体生存率80%,有效缓解率60%(2例死亡,2例PD,3例PR,3例CR);36个月总体生存率50%,有效缓解率30%(5例死亡,2例PD,3例CR)。结论 异体NK细胞治疗肝恶性肿瘤临床安全性良好,可提高患者短期生活质量,改善临床症状,在肝恶性肿瘤的治疗中具有一定的临床应用价值。

关键词: NK细胞, 细胞治疗, 肝恶性肿瘤

Abstract: Objective To observe the safety and efficacy of natural killer (NK) cell transfusion in the treatment of malignant liver tumors. Methods Ten patients with malignant liver tumors that had been treated by operation, transcatheter arterial chemoembolization (TACE) or microwave ablation were enrolled in this study. They received transfusion therapy with NK cells derived from their immediate family. The safety and short-term efficacy of this treatment was evaluated by observing the patients’response to transfused allogeneic NK cells, and the changes of life quality (KPS score),liver and kidney function, blood routine, circulating tumor cells (CTC),overall remission rate, overall survival rate and other indicators before and after the treatment. Results (1) After allogenic NK cell transfusion, one patient developed chills with chest tightness at half an hour post cell infusion and received symptomatic treatment. After 15 minutes, the symptoms were relieved and the temperature rose to the highest of 39.9℃, accompanied by nausea and vomiting. After being treated with Metoclopramide and Tylenol, the symptoms gradually disappeared and there was mild muscle soreness at the next day. One case had insomnia. The mental, appetite and physical strength of 5 patients improved significantly;(2) The number of CTC measured at 24 hours after infusion in 10 patients was lower than that before transfusion and the difference was statistically significant (P< 0.05). There was no significant change in liver and renal function;(3) Patients were followed up for 3 ~ 36 months. According to the Response Evaluation Criteria in Solid Tumors (mRECIST:complete response=CR,partial response=PR,stable disease=SD;progressive disease=PD), the 3-month overall survival rate was 100%,effective response rate was 80%(no death,2SD,3PR, 5CR); the 6-month overall survival rate was 90%,effective Response rate was 80%(1 death,1PD,3PR,5CR);overall survival rate at 12 months was 80%,effective response rate was 60% (2deaths,2PD,3PR,3CR);overall survival rate at 36 months was 50%, and effective response rate was 30% (5 deaths,2PD,3CR). Conclusion NK cells transfusion in the treatment of malignant liver tumors has good clinical safety. The treatment may improve the short-term quality of patients’ life, improve clinical symptoms and thus has certain clinical value in the treatment of malignant liver tumors.

Key words: Natural killer cell, Cell therapy, Liver malignant tumors