Adoptive Immunotherapy With Liver Allograft-Derived NK Cells Improves Recurrence-Free Survival After Living-Donor Liver Transplantation in Patients With Hepatocellular Carcinoma
Department of Gastroenterological and Transplant Surgery, Hiroshima University, Hiroshima, Japan.
Meeting: 2015 American Transplant Congress
Abstract number: 317
Keywords: Hepatocellular carcinoma, Liver transplantation, Natural killer cells, Tumor recurrence
Session Information
Session Name: Concurrent Session: Liver Transplantation for Hepatocellular Carcinoma
Session Type: Concurrent Session
Date: Monday, May 4, 2015
Session Time: 4:00pm-5:30pm
Presentation Time: 5:12pm-5:24pm
Location: Room 113-BC
Introduction: Previous studies revealed that the recurrence rate of hepatocellular carcinoma (HCC) was still 1020%, even among liver transplantation (LT) recipients meeting the Milan criteria (MC), which was probably due to occasional discrepancies between radiological imaging findings and the pathological stage. To minimize recurrence after LT, we have proposed using adjuvant immunotherapy with IL-2/anti-CD3 mAb-treated NK cells extracted from donor liver allograft; these cells express high levels of TRAIL and display vigorous cytotoxicity against HCC. We performed a phase I clinical study of this immunotherapy in LT recipients with HCC between 2006 and 2013.
Method: Twenty-four patients with HCC who met the MC, as determined using radiological staging, were enrolled in this study. Liver mononuclear cells extracted from perfusates of donor allografts were cultured with IL-2 for 3 days, and anti-CD3 mAb was added one day before administration of the cells to prevent GVHD. The final product was intravenously administered to the recipients 4 days after LT. We conducted a case-control study comparing the 24 recipients of immunotherapy (group I) to a control group of 25 period/stage-matched recipients who did not receive immunotherapy (group C).
Results: We administered a median of 273.5 million cells/patient. The 5-year recurrence-free survival (5Y-RFS) and 5-year overall survival (5Y-OS) rates of the study patients were 74.5% and 82.6%, respectively (median follow-up period, 4.7 years). The administration of the activated liver NK cells was completed without any safety issues. The incidence of severe postoperative adverse events was not associated with the inoculated cell dose. Among the case-control study cohort, 18 of 49 recipients exceeded the MC with respect to the pathology of the explant liver (11 in group I and 7 in group C). None of the HCC patients meeting pathological MC showed evidence of recurrence. Among patients with a pathological stage exceeding the MC, both the 5Y-RFS and 5Y-OS rates were significantly better in group I compared to group C (p = 0.006 and 0.013, respectively).
Conclusion: Adoptive immunotherapy with liver allograft-derived NK cells can be safely performed and may improve recurrence-free survival in HCC patients who radiologically meet but pathologically exceed the MC for living-donor LT.
To cite this abstract in AMA style:
Tanimine N, Tanaka Y, Ishiyama K, Ohira M, Shimizu S, Yano T, Ohdan H. Adoptive Immunotherapy With Liver Allograft-Derived NK Cells Improves Recurrence-Free Survival After Living-Donor Liver Transplantation in Patients With Hepatocellular Carcinoma [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/adoptive-immunotherapy-with-liver-allograft-derived-nk-cells-improves-recurrence-free-survival-after-living-donor-liver-transplantation-in-patients-with-hepatocellular-carcinoma/. Accessed November 8, 2024.« Back to 2015 American Transplant Congress