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Phase 1 clinical study of cell therapy with effective-mononuclear cells (E-MNC) for radiogenic xerostomia (first-in-human study) (FIH study on E-MNC therapy for radiogenic xerostomia)
BACKGROUND: Treatment for most patients with head and neck cancers includes ionizing radiation with or without chemotherapy. This treatment causes irreversible damage to salivary glands in the irradiation field accompanied by a loss of fluid-secreting acinar cells and a considerable decrease of sali...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Wolters Kluwer Health
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7328916/ https://www.ncbi.nlm.nih.gov/pubmed/32590759 http://dx.doi.org/10.1097/MD.0000000000020788 |
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author | Sumita, Yoshinori Iwamoto, Naoki Seki, Makoto Yoshida, Takako Honma, Ryo Iwatake, Mayumi Ohba, Seigo Takashi, I. Hotokezaka, Yuka Harada, Hiroshi Kuroshima, Shinichiro Nagai, Kazuhiro Asahara, Takayuki Atsushi Kawakam, I Asahina, Izumi |
author_facet | Sumita, Yoshinori Iwamoto, Naoki Seki, Makoto Yoshida, Takako Honma, Ryo Iwatake, Mayumi Ohba, Seigo Takashi, I. Hotokezaka, Yuka Harada, Hiroshi Kuroshima, Shinichiro Nagai, Kazuhiro Asahara, Takayuki Atsushi Kawakam, I Asahina, Izumi |
author_sort | Sumita, Yoshinori |
collection | PubMed |
description | BACKGROUND: Treatment for most patients with head and neck cancers includes ionizing radiation with or without chemotherapy. This treatment causes irreversible damage to salivary glands in the irradiation field accompanied by a loss of fluid-secreting acinar cells and a considerable decrease of saliva secretion. There is currently no adequate conventional treatment for this condition. In recent years, we developed an effective culture method to enhance the anti-inflammatory and vasculogenic phenotypes of peripheral blood mononuclear cells (PBMNCs), and such effectively conditioned PBMNC (E-MNC) therapy has shown promising improvements to the function of radiation-injured salivary glands in preclinical studies. However, the safety and effect of E-NMC therapy have yet assessed in human. The objective of this ongoing first-in-man study is to assess the safety, tolerability, and in part the efficacy of E-MNC therapy for treating radiation-induced xerostomia. METHODS/DESIGN: This phase 1 first-in-man study is an open-label, single-center, two-step dose escalation study. A total of 6 patients, who had no recurrence of head and neck cancer over 5 years following radiation therapy and suffered from radiation-induced xerostomia, will receive a transplantation of E-NMCs derived from autologous PBMNCs to a submandibular gland. The duration of the intervention will be 1 year. To analyze the recovery of salivary secretion, a gum test will be performed. To analyze the recovery of atrophic salivary glands, computed tomography (CT), and magnetic resonance imaging (MRI) of salivary glands will be conducted. The primary endpoint is the safety of the protocol. The secondary endpoints are the changes from baseline in whole saliva secretion and salivary gland atrophy. DISCUSSION: This will be the first clinical study of regenerative therapy using E-MNCs for patients with severe radiation-induced xerostomia. The results of this study are expected to contribute to developing the low-invasive cell-based therapy for radiation-induced xerostomia. TRIAL REGISTRATION: This study was registered with the Japan Registry of Clinical Trials (http://jrct.niph.go.jp) as jRCTb070190057. |
format | Online Article Text |
id | pubmed-7328916 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Wolters Kluwer Health |
record_format | MEDLINE/PubMed |
spelling | pubmed-73289162020-07-09 Phase 1 clinical study of cell therapy with effective-mononuclear cells (E-MNC) for radiogenic xerostomia (first-in-human study) (FIH study on E-MNC therapy for radiogenic xerostomia) Sumita, Yoshinori Iwamoto, Naoki Seki, Makoto Yoshida, Takako Honma, Ryo Iwatake, Mayumi Ohba, Seigo Takashi, I. Hotokezaka, Yuka Harada, Hiroshi Kuroshima, Shinichiro Nagai, Kazuhiro Asahara, Takayuki Atsushi Kawakam, I Asahina, Izumi Medicine (Baltimore) 3700 BACKGROUND: Treatment for most patients with head and neck cancers includes ionizing radiation with or without chemotherapy. This treatment causes irreversible damage to salivary glands in the irradiation field accompanied by a loss of fluid-secreting acinar cells and a considerable decrease of saliva secretion. There is currently no adequate conventional treatment for this condition. In recent years, we developed an effective culture method to enhance the anti-inflammatory and vasculogenic phenotypes of peripheral blood mononuclear cells (PBMNCs), and such effectively conditioned PBMNC (E-MNC) therapy has shown promising improvements to the function of radiation-injured salivary glands in preclinical studies. However, the safety and effect of E-NMC therapy have yet assessed in human. The objective of this ongoing first-in-man study is to assess the safety, tolerability, and in part the efficacy of E-MNC therapy for treating radiation-induced xerostomia. METHODS/DESIGN: This phase 1 first-in-man study is an open-label, single-center, two-step dose escalation study. A total of 6 patients, who had no recurrence of head and neck cancer over 5 years following radiation therapy and suffered from radiation-induced xerostomia, will receive a transplantation of E-NMCs derived from autologous PBMNCs to a submandibular gland. The duration of the intervention will be 1 year. To analyze the recovery of salivary secretion, a gum test will be performed. To analyze the recovery of atrophic salivary glands, computed tomography (CT), and magnetic resonance imaging (MRI) of salivary glands will be conducted. The primary endpoint is the safety of the protocol. The secondary endpoints are the changes from baseline in whole saliva secretion and salivary gland atrophy. DISCUSSION: This will be the first clinical study of regenerative therapy using E-MNCs for patients with severe radiation-induced xerostomia. The results of this study are expected to contribute to developing the low-invasive cell-based therapy for radiation-induced xerostomia. TRIAL REGISTRATION: This study was registered with the Japan Registry of Clinical Trials (http://jrct.niph.go.jp) as jRCTb070190057. Wolters Kluwer Health 2020-06-26 /pmc/articles/PMC7328916/ /pubmed/32590759 http://dx.doi.org/10.1097/MD.0000000000020788 Text en Copyright © 2020 the Author(s). Published by Wolters Kluwer Health, Inc. http://creativecommons.org/licenses/by/4.0 This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0 |
spellingShingle | 3700 Sumita, Yoshinori Iwamoto, Naoki Seki, Makoto Yoshida, Takako Honma, Ryo Iwatake, Mayumi Ohba, Seigo Takashi, I. Hotokezaka, Yuka Harada, Hiroshi Kuroshima, Shinichiro Nagai, Kazuhiro Asahara, Takayuki Atsushi Kawakam, I Asahina, Izumi Phase 1 clinical study of cell therapy with effective-mononuclear cells (E-MNC) for radiogenic xerostomia (first-in-human study) (FIH study on E-MNC therapy for radiogenic xerostomia) |
title | Phase 1 clinical study of cell therapy with effective-mononuclear cells (E-MNC) for radiogenic xerostomia (first-in-human study) (FIH study on E-MNC therapy for radiogenic xerostomia) |
title_full | Phase 1 clinical study of cell therapy with effective-mononuclear cells (E-MNC) for radiogenic xerostomia (first-in-human study) (FIH study on E-MNC therapy for radiogenic xerostomia) |
title_fullStr | Phase 1 clinical study of cell therapy with effective-mononuclear cells (E-MNC) for radiogenic xerostomia (first-in-human study) (FIH study on E-MNC therapy for radiogenic xerostomia) |
title_full_unstemmed | Phase 1 clinical study of cell therapy with effective-mononuclear cells (E-MNC) for radiogenic xerostomia (first-in-human study) (FIH study on E-MNC therapy for radiogenic xerostomia) |
title_short | Phase 1 clinical study of cell therapy with effective-mononuclear cells (E-MNC) for radiogenic xerostomia (first-in-human study) (FIH study on E-MNC therapy for radiogenic xerostomia) |
title_sort | phase 1 clinical study of cell therapy with effective-mononuclear cells (e-mnc) for radiogenic xerostomia (first-in-human study) (fih study on e-mnc therapy for radiogenic xerostomia) |
topic | 3700 |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7328916/ https://www.ncbi.nlm.nih.gov/pubmed/32590759 http://dx.doi.org/10.1097/MD.0000000000020788 |
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