Pilot study to determine the safety and feasibility of deceased donor liver natural killer cell infusion to liver transplant recipients with hepatocellular carcinoma

Masahiro Ohira, Ryuichi Hotta, Yuka Tanaka, Toshiharu Matsuura, Akin Tekin, Gennaro Selvaggi, Rodrigo Vianna, Camillo Ricordi, Phillip Ruiz, Seigo Nishida, Andreas G. Tzakis, Hideki Ohdan

Research output: Contribution to journalArticlepeer-review

Abstract

Liver transplantation (LT) is a viable treatment option for cirrhosis patients with hepatocellular carcinoma (HCC). However, recurrence is the rate-limiting factor of long-term survival. To prevent this, we conducted the phase I study of the adoptive transfer of deceased donor liver-derived natural killer (NK) cells. Liver NK cells were extracted from donor liver graft perfusate and were stimulated in vitro with IL-2. The patient received an intravenous infusion of NK cells 3–5 days after LT. Eighteen LT recipients were treated. There were no severe cell infusion-related adverse events or acute rejection episodes. One patient withdrew from the study because the pathological observation revealed sarcoma instead of HCC. All patients who received this immunotherapy completed the follow-up for at least 2 years without evidence of HCC recurrence (median follow-up, 96 months [range, 17–121 months]). Considering that 9 (52.9%) of the 17 patients pathologically exceeded the Milan criteria, liver NK cell infusion is likely to be useful for preventing HCC recurrence after LT. This is the first-in-human immunotherapy study using deceased donor liver-derived NK cells to prevent HCC recurrence after LT. This treatment was well tolerated and resulted in no HCC recurrence after LT. Clinical trial registration www.clinicaltrials.gov; NCT01147380; registration date: June 17, 2010.

Original languageEnglish (US)
JournalCancer Immunology, Immunotherapy
DOIs
StateAccepted/In press - 2021

Keywords

  • HCC
  • Immunotherapy
  • Liver transplantation
  • NK cell

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Cancer Research

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