辅助免疫自体细胞因子诱导的杀伤细胞肝癌

StephenW

Adjuvant Immunotherapy With Autologous Cytokine-Induced Killer Cells for Hepatocellular Carcinoma
Joon Hyeok Lee∗
, Jeong-Hoon Lee∗
, Young-Suk Lim
, Jong Eun Yeon
, Tae-Jin Song
, Su Jong Yu
, Geum-Youn Gwak
, Kang Mo Kim
, Yoon Jun Kim
, Jae Won Lee
, Jung-Hwan Yooncorrespondenceemail
∗Authors share co-first authorship.
Open Access Article has an altmetric score of 4
DOI: http://dx.doi.org/10.1053/j.gastro.2015.02.055 |

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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 × 109 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.
Keywords:
Liver Cancer, Clinical Trial, IL2, NK Cell
Abbreviations used in this paper:
AE (adverse event), CI (confidence interval), CIK (cytokine-induced killer), HBV (hepatitis B virus), HCC (hepatocellular carcinoma), HR (hazard ratio), IL2 (interleukin 2), MHC (major histocompatibility complex), NK (natural killer), OS (overall survival), PEI (percutaneous ethanol injection), RFA (radiofrequency ablation), RFS (recurrence-free survival)

StephenW

辅助免疫自体细胞因子诱导的杀伤细胞肝癌
俊赫李*
，政勋李*
，英淑林
，金正恩妍
，泰金松
苏钟宇
，今，郭氏妍
康默金
，尹金俊
，在元利
，郑焕Yooncorrespondenceemail
*作者分享共同第一作者。
开放获取文章的altmetric比分4
DOI：http://dx.doi.org/10.1053/j.gastro.2015.02.055 |

经笔者资助开放获取（S）
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背景与目的

没有辅助治疗已经显示出延长患者的肝细胞癌（HCC）接受根治性治疗的生存。我们调查是否激活细胞因子诱导杀伤（CIK）细胞的注射（CD3 + / CD56 +和CD3 + / CD56- T细胞和CD3- / CD56 +自然杀伤细胞）延长患者根治疗法肝癌后无复发存活。
方法

我们进行了一项多中心，随机，开放标记，相位的功效和佐剂的免疫治疗的安全性的3试验与活化CIK细胞（由患者的外周血单核细胞的培养用白细胞介素2中，创建和抗CD3抗体）。该研究共纳入230例肝癌手术切除，射频消融，或无水乙醇注射在韩国大学附属医院治疗。患者被随机分配接受免疫治疗（注射6.4×109自体CIK细胞，在60周16倍）或无辅助治疗（控制）。主要终点是无复发生存期;次要终点包括总生存期，癌症特异性生存和安全。
结果

无复发生存中位时间为免疫治疗组在44.0个月30.0个月，对照组（免疫疗法危害比，0.63; 95％置信区间[CI]，0.43-0.94; P = 0.010由单面log-rank检验）。危险比也较低，在免疫比对照组全因死亡（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）。甲显著较高比例的患者的免疫治疗组比对照组有一个不利的事件（62％比41％; P = 0.002），但患者的严重不良事件的比例没有组之间显著差异（7.8％ VS 3.5％，P = 0.15）。
结论

在谁接受根治性治疗的肝癌患者，辅助免疫激活与CIK细胞增加无复发生存率和总生存率。 ClinicalTrials.gov编号：NCT00699816。
关键词：
肝癌，临床试验，IL2，NK细胞
在本文中使用的缩写：
AE（不良事件），CI（置信区间），CIK（细胞因子诱导的杀伤），HBV（乙肝病毒），肝癌（肝癌），人力资源（危险比），IL2（白介素2），MHC（主要组织相容性复合），NK（自然杀伤），OS（总生存），PEI（无水酒精注射），射频消融（射频消融），RFS（无复发生存率）