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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.

Author information

1
Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
2
Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea.
3
Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
4
The Liver Center, Korea University Guro Hospital, Seoul, Korea.
5
Department of Surgery, Korea University Ansan Hospital, Ansan, Gyeonggi-do, Korea.
6
Department of Statistics, Korea University, Seoul, Korea.
7
Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea. Electronic address: yoonjh@snu.ac.kr.

Abstract

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 × 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.

KEYWORDS:

Clinical Trial; IL2; Liver Cancer; NK Cell

PMID:
25747273
DOI:
10.1053/j.gastro.2015.02.055
[Indexed for MEDLINE]
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