A phase I/II study of adoptive immunotherapy using donor liver graft-derived NK cell-enriched immune cells to prevent severe infection after liver transplantation.

Bloodstream infections (BSIs) are significant postoperative complications associated with high mortality rates after liver transplantation (LT). Natural killer (NK) cells, which are key components of the innate immune system, have demonstrated potential to combat both infections and cancer. The use...

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Main Authors: Masahiro Ohira, Yuki Imaoka, Koki Sato, Koki Imaoka, Tomoaki Bekki, Takuya Yano, Ryosuke Nakano, Hiroshi Sakai, Shintaro Kuroda, Hiroyuki Tahara, Kentaro Ide, Tsuyoshi Kobayashi, Yuka Tanaka, Junko Tanaka, Hideki Ohdan
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2025-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0313102
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author Masahiro Ohira
Yuki Imaoka
Koki Sato
Koki Imaoka
Tomoaki Bekki
Takuya Yano
Ryosuke Nakano
Hiroshi Sakai
Shintaro Kuroda
Hiroyuki Tahara
Kentaro Ide
Tsuyoshi Kobayashi
Yuka Tanaka
Junko Tanaka
Hideki Ohdan
author_facet Masahiro Ohira
Yuki Imaoka
Koki Sato
Koki Imaoka
Tomoaki Bekki
Takuya Yano
Ryosuke Nakano
Hiroshi Sakai
Shintaro Kuroda
Hiroyuki Tahara
Kentaro Ide
Tsuyoshi Kobayashi
Yuka Tanaka
Junko Tanaka
Hideki Ohdan
author_sort Masahiro Ohira
collection DOAJ
description Bloodstream infections (BSIs) are significant postoperative complications associated with high mortality rates after liver transplantation (LT). Natural killer (NK) cells, which are key components of the innate immune system, have demonstrated potential to combat both infections and cancer. The use of activated NK cells to mitigate post-LT infections, particularly BSIs, has attracted considerable interest. We conducted a single-arm Phase I/II clinical trial to evaluate the safety and efficacy of transfusing donor liver-derived NK cells into LT recipients. Patients were administered a single infusion of these NK cells three days post-LT. The primary endpoint was BSI incidence. This study was terminated in 19 patients because of the high incidence of BSIs. Of the 19 patients receiving immunotherapy, six (31.5%) developed BSIs within one month of LT. No adverse events were directly related to NK cell infusion. Acute rejection was noted in seven patients (36.8%). After infusion, NK cell activity in the recipient's peripheral blood remained stable. In conclusion, this clinical trial did not reach the primary endpoint. This could be attributed to a significant percentage of patients presenting with high immunological risk. Nonetheless, the infusion procedure demonstrated a favorable safety profile without serious adverse events.
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spelling doaj-art-3243c0fd071c4a90ae5ae84edc4d34b12025-08-20T03:32:53ZengPublic Library of Science (PLoS)PLoS ONE1932-62032025-01-01201e031310210.1371/journal.pone.0313102A phase I/II study of adoptive immunotherapy using donor liver graft-derived NK cell-enriched immune cells to prevent severe infection after liver transplantation.Masahiro OhiraYuki ImaokaKoki SatoKoki ImaokaTomoaki BekkiTakuya YanoRyosuke NakanoHiroshi SakaiShintaro KurodaHiroyuki TaharaKentaro IdeTsuyoshi KobayashiYuka TanakaJunko TanakaHideki OhdanBloodstream infections (BSIs) are significant postoperative complications associated with high mortality rates after liver transplantation (LT). Natural killer (NK) cells, which are key components of the innate immune system, have demonstrated potential to combat both infections and cancer. The use of activated NK cells to mitigate post-LT infections, particularly BSIs, has attracted considerable interest. We conducted a single-arm Phase I/II clinical trial to evaluate the safety and efficacy of transfusing donor liver-derived NK cells into LT recipients. Patients were administered a single infusion of these NK cells three days post-LT. The primary endpoint was BSI incidence. This study was terminated in 19 patients because of the high incidence of BSIs. Of the 19 patients receiving immunotherapy, six (31.5%) developed BSIs within one month of LT. No adverse events were directly related to NK cell infusion. Acute rejection was noted in seven patients (36.8%). After infusion, NK cell activity in the recipient's peripheral blood remained stable. In conclusion, this clinical trial did not reach the primary endpoint. This could be attributed to a significant percentage of patients presenting with high immunological risk. Nonetheless, the infusion procedure demonstrated a favorable safety profile without serious adverse events.https://doi.org/10.1371/journal.pone.0313102
spellingShingle Masahiro Ohira
Yuki Imaoka
Koki Sato
Koki Imaoka
Tomoaki Bekki
Takuya Yano
Ryosuke Nakano
Hiroshi Sakai
Shintaro Kuroda
Hiroyuki Tahara
Kentaro Ide
Tsuyoshi Kobayashi
Yuka Tanaka
Junko Tanaka
Hideki Ohdan
A phase I/II study of adoptive immunotherapy using donor liver graft-derived NK cell-enriched immune cells to prevent severe infection after liver transplantation.
PLoS ONE
title A phase I/II study of adoptive immunotherapy using donor liver graft-derived NK cell-enriched immune cells to prevent severe infection after liver transplantation.
title_full A phase I/II study of adoptive immunotherapy using donor liver graft-derived NK cell-enriched immune cells to prevent severe infection after liver transplantation.
title_fullStr A phase I/II study of adoptive immunotherapy using donor liver graft-derived NK cell-enriched immune cells to prevent severe infection after liver transplantation.
title_full_unstemmed A phase I/II study of adoptive immunotherapy using donor liver graft-derived NK cell-enriched immune cells to prevent severe infection after liver transplantation.
title_short A phase I/II study of adoptive immunotherapy using donor liver graft-derived NK cell-enriched immune cells to prevent severe infection after liver transplantation.
title_sort phase i ii study of adoptive immunotherapy using donor liver graft derived nk cell enriched immune cells to prevent severe infection after liver transplantation
url https://doi.org/10.1371/journal.pone.0313102
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