Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea.
Gastroenterology. 2015 Jun;148(7):1383-91.e6. doi: 10.1053/j.gastro.2015.02.055. Epub 2015 Mar 4.
BACKGROUND & AIMS: No adjuvant therapy has been shown to extend the survival of patients with hepatocellular carcinoma (HCC) receiving curative treatment. We investigated whether injections of activated cytokine-induced killer (CIK) cells (CD3+/CD56+ and CD3+/CD56- T cells and CD3-/CD56+ natural killer cells) prolongs recurrence-free survival of patients after curative therapy for HCC.
We performed a multicenter, randomized, open-label, phase 3 trial of the efficacy and safety of adjuvant immunotherapy with activated CIK cells (created by incubation of patients' peripheral blood mononuclear cells with interleukin 2 and an antibody against CD3). The study included 230 patients with HCC treated by surgical resection, radiofrequency ablation, or percutaneous ethanol injection at university-affiliated hospitals in Korea. Patients were assigned randomly to receive immunotherapy (injection of 6.4 × 10(9) autologous CIK cells, 16 times during 60 weeks) or no adjuvant therapy (controls). The primary end point was recurrence-free survival; secondary end points included overall survival, cancer-specific survival, and safety.
The median time of recurrence-free survival was 44.0 months in the immunotherapy group and 30.0 months in the control group (hazard ratio with immunotherapy, 0.63; 95% confidence interval [CI], 0.43-0.94; P = .010 by 1-sided log-rank test). Hazard ratios also were lower in the immunotherapy than in the control group for all-cause death (0.21; 95% CI, 0.06-0.75; P = .008) and cancer-related death (0.19; 95% CI, 0.04-0.87; P = .02). A significantly higher proportion of patients in the immunotherapy group than in the control group had an adverse event (62% vs 41%; P = .002), but the proportion of patients with serious adverse events did not differ significantly between groups (7.8% vs 3.5%; P = .15).
In patients who underwent curative treatment for HCC, adjuvant immunotherapy with activated CIK cells increased recurrence-free and overall survival. ClinicalTrials.gov number: NCT00699816.
目前尚无辅助治疗方法可延长接受根治性治疗的肝细胞癌（HCC）患者的生存时间。我们研究了细胞因子诱导的杀伤（CIK）细胞（CD3+/CD56+和 CD3+/CD56- T 细胞以及 CD3-/CD56+自然杀伤细胞）的注射是否会延长 HCC 患者根治性治疗后的无复发生存时间。
我们进行了一项多中心、随机、开放标签、3 期临床试验，评估了辅助免疫疗法（使用白细胞介素 2 和抗 CD3 抗体孵育患者外周血单个核细胞以生成激活的 CIK 细胞）对 HCC 患者的疗效和安全性。该研究纳入了在韩国大学附属医院接受手术切除、射频消融或经皮乙醇注射治疗的 230 例 HCC 患者。患者被随机分配接受免疫治疗（注射 6.4×109 个自体 CIK 细胞，60 周内注射 16 次）或不接受辅助治疗（对照组）。主要终点为无复发生存；次要终点包括总生存、癌症特异性生存和安全性。
免疫治疗组的中位无复发生存时间为 44.0 个月，对照组为 30.0 个月（免疫治疗组的风险比为 0.63；95%置信区间 [CI]，0.43-0.94；单侧对数秩检验 P=0.010）。免疫治疗组的全因死亡风险（0.21；95%CI，0.06-0.75；P=0.008）和癌症相关死亡风险（0.19；95%CI，0.04-0.87；P=0.02）也均低于对照组。与对照组相比，免疫治疗组发生不良事件的患者比例更高（62% vs 41%；P=0.002），但两组严重不良事件的比例无显著差异（7.8% vs 3.5%；P=0.15）。
在接受 HCC 根治性治疗的患者中，辅助免疫疗法（使用白细胞介素 2 和抗 CD3 抗体孵育患者外周血单个核细胞以生成激活的 CIK 细胞）可提高无复发生存率和总生存率。临床试验注册编号：NCT00699816。
