@article{311c92e17cec4e16b954e79f4224cb62,
title = "Adjuvant immunotherapy with autologous cytokine-induced killer cells for hepatocellular carcinoma",
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.",
keywords = "Clinical Trial, IL2, Liver Cancer, NK Cell",
author = "Lee, {Joon Hyeok} and Lee, {Jeong Hoon} and Lim, {Young Suk} and Yeon, {Jong Eun} and Song, {Tae Jin} and Yu, {Su Jong} and Gwak, {Geum Youn} and Kim, {Kang Mo} and Kim, {Yoon Jun} and Lee, {Jae Won} and Yoon, {Jung Hwan}",
note = "Funding Information: Conflicts of interest These authors disclose the following: Joon Hyeok Lee has received grants from Green Cross Cell Corp, Bukwang Pharmaceuticals, Pfizer, JW Creagene, and GlaxoSmithKline, has received lecture fees from Bayer Pharmaceuticals, Gilead Science, Bukwang Pharmaceuticals, and GlaxoSmithKline, and serves as an advisory board member of Gilead Science and Bristol-Myers Squibb; Jung-Hwan Yoon has received a research grant from Bayer HealthCare Pharmaceuticals; Young-Suk Lim has received research grants from Bayer HealthCare Pharmaceuticals and Gilead Science; Jong Eun Yeon has received research grants from Yuhan Pharmaceuticals and Jeil Pharmaceuticals, and serves as an advisory board member of Bayer Korea; Yoon Jun Kim has received research grants from Bristol-Myers Squibb, Roche, JW Creagene, Bukwang Pharmaceuticals, Handok Pharmaceuticals, Hanmi Pharmaceuticals, Yuhan Pharmaceuticals, and Pharmaking, and has received lecture fees from Bayer HealthCare Pharmaceuticals, Gilead Science, MSD Korea, Yuhan Pharmaceuticals, Samil Pharmaceuticals, CJ Pharmaceuticals, Bukwang Pharmaceuticals, and Handok Pharmaceuticals; Kang Mo Kim has received research grants from AstraZeneca, Yuhan Pharmaceuticals, and Il-Dong Pharmaceuticals, has received lecture fees from Bayer HealthCare Pharmaceuticals, MSD, and GlaxoSmithKline, and has received a consulting fee from Bayer HealthCare Pharmaceuticals; Geum-Youn Gwak has received lecture fees from Bristol-Myers Squibb, JW Creagene, Handok Pharmaceuticals, and MSD Korea; and Su Jong Yu has received a lecture fee from Bayer HealthCare Pharmaceuticals. The remaining authors disclose no conflicts. Funding Information: Funding Supported by Green Cross Cell Corp (Seoul, Korea). This study was designed by the sponsor in conjunction with the principal academic investigators. Data were managed in parallel by the sponsor and the principal investigators. Publisher Copyright: {\textcopyright} 2015 AGA Institute.",
year = "2015",
month = jun,
day = "1",
doi = "10.1053/j.gastro.2015.02.055",
language = "English",
volume = "148",
pages = "1383--1391.e6",
journal = "Gastroenterology",
issn = "0016-5085",
publisher = "W.B. Saunders Ltd",
number = "7",
}