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

Joon Hyeok Lee, Jeong Hoon Lee, Young Suk Lim, Jong Eun Yeon, Taejin Song, Su Jong Yu, Geum Youn Gwak, Kang Mo Kim, Yoon Jun Kim, Jae Won Lee, Jung Hwan Yoon

Research output: Contribution to journalArticle

150 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 Jan 1

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Cytokine-Induced Killer Cells
Immunotherapy
Hepatocellular Carcinoma
Survival
Recurrence
Confidence Intervals
Control Groups
Injections
Therapeutics
Safety
Korea
Natural Killer Cells
Interleukin-2
Cause of Death
Blood Cells
Neoplasms
Ethanol
T-Lymphocytes

Keywords

  • Clinical Trial
  • IL2
  • Liver Cancer
  • NK Cell

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Adjuvant immunotherapy with autologous cytokine-induced killer cells for hepatocellular carcinoma. / Lee, Joon Hyeok; Lee, Jeong Hoon; Lim, Young Suk; Yeon, Jong Eun; Song, Taejin; Yu, Su Jong; Gwak, Geum Youn; Kim, Kang Mo; Kim, Yoon Jun; Lee, Jae Won; Yoon, Jung Hwan.

In: Gastroenterology, Vol. 148, No. 7, 01.01.2015, p. 1383-1391.e6.

Research output: Contribution to journalArticle

Lee, JH, Lee, JH, Lim, YS, Yeon, JE, Song, T, Yu, SJ, Gwak, GY, Kim, KM, Kim, YJ, Lee, JW & Yoon, JH 2015, 'Adjuvant immunotherapy with autologous cytokine-induced killer cells for hepatocellular carcinoma', Gastroenterology, vol. 148, no. 7, pp. 1383-1391.e6. https://doi.org/10.1053/j.gastro.2015.02.055
Lee, Joon Hyeok ; Lee, Jeong Hoon ; Lim, Young Suk ; Yeon, Jong Eun ; Song, Taejin ; Yu, Su Jong ; Gwak, Geum Youn ; Kim, Kang Mo ; Kim, Yoon Jun ; Lee, Jae Won ; Yoon, Jung Hwan. / Adjuvant immunotherapy with autologous cytokine-induced killer cells for hepatocellular carcinoma. In: Gastroenterology. 2015 ; Vol. 148, No. 7. pp. 1383-1391.e6.
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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.",
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AU - Lee, Joon Hyeok

AU - Lee, Jeong Hoon

AU - Lim, Young Suk

AU - Yeon, Jong Eun

AU - Song, Taejin

AU - Yu, Su Jong

AU - Gwak, Geum Youn

AU - Kim, Kang Mo

AU - Kim, Yoon Jun

AU - Lee, Jae Won

AU - Yoon, Jung Hwan

PY - 2015/1/1

Y1 - 2015/1/1

N2 - 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.

AB - 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.

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KW - Liver Cancer

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