Adoptive immunotherapy with natural killer cells from peripheral blood CD34+ stem cells to prevent hepatocellular carcinoma recurrence after curative hepatectomy: a study protocol for an open-label, single-arm phase I study
Kenichi Yoshimura,
Keiko Ueda,
Hiroshi Aikata,
Michio Imamura,
Reo Kawano,
Masahiro Ohira,
Tsuyoshi Kobayashi,
Yuka Tanaka,
Yuki Imaoka,
Koki Sato,
Koki Imaoka,
Ryosuke Nakano,
Marlen Doskali,
Jinlian Piao,
Mayuna Nakamura,
Tetsumi Yoshida,
Tatsuo Ichinohe,
Natsuko Tamura,
Taizo Hirata,
Naoki Tanimine,
Shintaro Kuroda,
Hiroyuki Tahara,
Kentaro Ide,
Hideki Ohdan
Affiliations
Kenichi Yoshimura
Center for Integrated Medical Research, Hiroshima University, Hiroshima, Japan
Keiko Ueda
1 Regulatory strategy Division,Clinical Research Support Center, The University of Tokyo Hospital, Tokyo, Japan
Hiroshi Aikata
7 Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
Michio Imamura
Laboratory for Digestive Diseases, Center for Genomic Medicine, RIKEN, Hiroshima, Japan
Reo Kawano
Clinical Research Center in Hiroshima, Hiroshima University Hospital, Hiroshima, Japan
Masahiro Ohira
Department of Gastroenterological and Transplant Surgery, Hiroshima University, Hiroshima, Japan
Tsuyoshi Kobayashi
Department of Gastroenterological and Transplant Surgery, Hiroshima University, Hiroshima, Japan
Yuka Tanaka
Department of Gastroenterological and Transplant Surgery, Hiroshima University, Hiroshima, Japan
Yuki Imaoka
Department of Gastroenterological and Transplant Surgery, Hiroshima University, Hiroshima, Japan
Koki Sato
Department of Gastroenterological and Transplant Surgery, Hiroshima University, Hiroshima, Japan
Koki Imaoka
Department of Gastroenterological and Transplant Surgery, Hiroshima University, Hiroshima, Japan
Ryosuke Nakano
Department of Gastroenterological and Transplant Surgery, Hiroshima University, Hiroshima, Japan
Marlen Doskali
Department of Gastroenterological and Transplant Surgery, Hiroshima University, Hiroshima, Japan
Jinlian Piao
Department of Gastroenterological and Transplant Surgery, Hiroshima University, Hiroshima, Japan
Mayuna Nakamura
Department of Gastroenterological and Transplant Surgery, Hiroshima University, Hiroshima, Japan
Tetsumi Yoshida
Department of Hematology and Oncology, Hiroshima University Hospital, Hiroshima, Japan
Tatsuo Ichinohe
Department of Hematology and Oncology, Hiroshima University Hospital, Hiroshima, Japan
Natsuko Tamura
Clinical Research Center, Hiroshima University Hospital, Hiroshima, Japan
Taizo Hirata
Clinical Research Center, Hiroshima University Hospital, Hiroshima, Japan
Naoki Tanimine
Department of Gastroenterological and Transplant Surgery, Hiroshima University, Hiroshima, Japan
Shintaro Kuroda
Department of Gastroenterological and Transplant Surgery, Hiroshima University, Hiroshima, Japan
Hiroyuki Tahara
Department of Gastroenterological and Transplant Surgery, Hiroshima University, Hiroshima, Japan
Kentaro Ide
Department of Gastroenterological and Transplant Surgery, Hiroshima University, Hiroshima, Japan
Hideki Ohdan
Department of Gastroenterological and Transplant Surgery, Hiroshima University, Hiroshima, Japan
Introduction Hepatocellular carcinoma (HCC) remains a major clinical problem as more than half of these cases recur after radical resection. Natural killer (NK) cells are at the forefront of the innate immune system and attack microcarcinomas and circulating tumour cells. The objective of this study was to evaluate the feasibility and toxicity of peripheral blood CD34+ stem cell-derived NK cell infusion after radical hepatectomy for HCC.Methods and analysis This is an open-label, single-arm, single-centre phase I study. Patients who have undergone initial hepatectomy for HCC with three or more risk factors for recurrence (≥10 ng/mL of Alpha fetoprotein (AFP), ≥360 mAU/mL of PIVKA-II, multiple tumours and ≥3 peripheral blood circulating tumour cells) will be enrolled and be treated with three peripheral blood CD34+ stem cell-derived NK cell infusions every 3 months. The primary endpoint will be safety assessment including the type and severity of adverse events, frequency of occurrence and duration of occurrence. The secondary endpoints will include survival, effect of immune response and clinical laboratory test results.Ethics and dissemination Ethical approval of the trial was obtained from the Certified Committee for Regenerative Medicine Hiroshima University in Japan. The trial results will be shared with the scientific community at international conferences and by publication in a peer-reviewed journal.Trial registration number jRCTb060200020.
