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Gastroenterology. 2015 Jun;148(7):1383-91.e6. doi: 10.1053/j.gastro.2015.02.055. Epub 2015 Mar 4.

Adjuvant immunotherapy with autologous cytokine-induced killer cells for hepatocellular carcinoma.

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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.
Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
The Liver Center, Korea University Guro Hospital, Seoul, Korea.
Department of Surgery, Korea University Ansan Hospital, Ansan, Gyeonggi-do, Korea.
Department of Statistics, Korea University, Seoul, Korea.
Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea. Electronic address:



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. number: NCT00699816.


Clinical Trial; IL2; Liver Cancer; NK Cell

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