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 Yoon

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    374 Citations (Scopus)

    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 × 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.

    Original languageEnglish
    Pages (from-to)1383-1391.e6
    JournalGastroenterology
    Volume148
    Issue number7
    DOIs
    Publication statusPublished - 2015 Jun 1

    Bibliographical note

    Publisher Copyright:
    © 2015 AGA Institute.

    Keywords

    • Clinical Trial
    • IL2
    • Liver Cancer
    • NK Cell

    ASJC Scopus subject areas

    • Hepatology
    • Gastroenterology

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