Adjuvant Immunotherapy With Autologous Cytokine-Induced Killer Cells for Hepatocellular Carcinoma
Adjuvant Immunotherapy With Autologous Cytokine-Induced Killer Cells for Hepatocellular Carcinoma
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DOI：
10.1053/j.gastro.2015.02.055
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发表时间：
2015-06-01
期刊：
影响因子：
29.4
通讯作者：
Yoon, Jung-Hwan
中科院分区：
文献类型：
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作者：
Lee, Joon Hyeok;Lee, Jeong-Hoon;Yoon, Jung-Hwan
背景与目的：没有辅助治疗已被证明可以延长接受根治性治疗的肝细胞癌（HCC）患者的生存期。我们研究了注射活化的苦参碱诱导的杀伤（CIK）细胞（CD 3 +/CD 56+和CD 3 +/CD 56-T细胞和CD 3-/CD 56+自然杀伤细胞）是否能提高肝癌根治性治疗后患者的无复发生存率。方法：我们进行了一项多中心，随机，开放标签，3期试验的有效性和安全性的辅助免疫治疗与活化CIK细胞（通过培养患者的外周血单核细胞与白细胞介素2和抗CD 3抗体）。该研究包括230名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）。主要终点是无复发生存期;次要终点包括总生存期、癌症特异性生存期和安全性。研究结果：免疫治疗组的中位无复发生存期为44.0个月，对照组为30.0个月（免疫治疗的风险比为0.63; 95%置信区间[CI]为0.43-0.94;单侧对数秩检验P = 0.010）。免疫治疗组的全因死亡（0.21; 95%CI，0.06-0.75; P = 0.008）和癌症相关死亡（0.19; 95%CI，0.04-0.87; P = 0.02）的风险比也低于对照组。免疫治疗组发生不良事件的患者比例显著高于对照组（62% vs 41%; P = 0.002），但两组发生严重不良事件的患者比例无显著差异（7.8% vs 3.5%; P = 0.15）。结论：在接受根治性治疗的HCC患者中，活化CIK细胞的辅助免疫治疗增加了无复发和总生存期。ClinicalTrials.gov编号：NCT 00699816。
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. METHODS: 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 x 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. RESULTS: 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). CONCLUSIONS: In patients who underwent curative treatment for HCC, adjuvant immunotherapy with activated CIK cells increased recurrence-free and overall survival. ClinicalTrials.gov number: NCT00699816.