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Phase I Clinical Trial of Fibronectin CH296-Stimulated T Cell Therapy in Patients with Advanced Cancer
BACKGROUND: Previous studies have demonstrated that less-differentiated T cells are ideal for adoptive T cell transfer therapy (ACT) and that fibronectin CH296 (FN-CH296) together with anti-CD3 resulted in cultured cells that contain higher amounts of less-differentiated T cells. In this phase I cli...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3908868/ https://www.ncbi.nlm.nih.gov/pubmed/24497917 http://dx.doi.org/10.1371/journal.pone.0083786 |
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author | Ishikawa, Takeshi Kokura, Satoshi Enoki, Tatsuji Sakamoto, Naoyuki Okayama, Tetsuya Ideno, Mitsuko Mineno, Junichi Uno, Kazuko Yoshida, Naohisa Kamada, Kazuhiro Katada, Kazuhiro Uchiyama, Kazuhiko Handa, Osamu Takagi, Tomohisa Konishi, Hideyuki Yagi, Nobuaki Naito, Yuji Itoh, Yoshito Yoshikawa, Toshikazu |
author_facet | Ishikawa, Takeshi Kokura, Satoshi Enoki, Tatsuji Sakamoto, Naoyuki Okayama, Tetsuya Ideno, Mitsuko Mineno, Junichi Uno, Kazuko Yoshida, Naohisa Kamada, Kazuhiro Katada, Kazuhiro Uchiyama, Kazuhiko Handa, Osamu Takagi, Tomohisa Konishi, Hideyuki Yagi, Nobuaki Naito, Yuji Itoh, Yoshito Yoshikawa, Toshikazu |
author_sort | Ishikawa, Takeshi |
collection | PubMed |
description | BACKGROUND: Previous studies have demonstrated that less-differentiated T cells are ideal for adoptive T cell transfer therapy (ACT) and that fibronectin CH296 (FN-CH296) together with anti-CD3 resulted in cultured cells that contain higher amounts of less-differentiated T cells. In this phase I clinical trial, we build on these prior results by assessing the safety and efficacy of FN-CH296 stimulated T cell therapy in patients with advanced cancer. METHODS: Patients underwent fibronectin CH296-stimulated T cell therapy up to six times every two weeks and the safety and antitumor activity of the ACT were assessed. In order to determine immune function, whole blood cytokine levels and the number of peripheral regulatory T cells were analyzed prior to ACT and during the follow up. RESULTS: Transferred cells contained numerous less-differentiated T cells greatly represented by CD27+CD45RA+ or CD28+CD45RA+ cell, which accounted for approximately 65% and 70% of the total, respectively. No ACT related severe or unexpected toxicities were observed. The response rate among patients was 22.2% and the disease control rate was 66.7%. CONCLUSIONS: The results obtained in this phase I trial, indicate that FN-CH296 stimulated T cell therapy was very well tolerated with a level of efficacy that is quite promising. We also surmise that expanding T cell using CH296 is a method that can be applied to other T- cell-based therapies. TRIAL REGISTRATION: UMIN UMIN000001835 |
format | Online Article Text |
id | pubmed-3908868 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-39088682014-02-04 Phase I Clinical Trial of Fibronectin CH296-Stimulated T Cell Therapy in Patients with Advanced Cancer Ishikawa, Takeshi Kokura, Satoshi Enoki, Tatsuji Sakamoto, Naoyuki Okayama, Tetsuya Ideno, Mitsuko Mineno, Junichi Uno, Kazuko Yoshida, Naohisa Kamada, Kazuhiro Katada, Kazuhiro Uchiyama, Kazuhiko Handa, Osamu Takagi, Tomohisa Konishi, Hideyuki Yagi, Nobuaki Naito, Yuji Itoh, Yoshito Yoshikawa, Toshikazu PLoS One Research Article BACKGROUND: Previous studies have demonstrated that less-differentiated T cells are ideal for adoptive T cell transfer therapy (ACT) and that fibronectin CH296 (FN-CH296) together with anti-CD3 resulted in cultured cells that contain higher amounts of less-differentiated T cells. In this phase I clinical trial, we build on these prior results by assessing the safety and efficacy of FN-CH296 stimulated T cell therapy in patients with advanced cancer. METHODS: Patients underwent fibronectin CH296-stimulated T cell therapy up to six times every two weeks and the safety and antitumor activity of the ACT were assessed. In order to determine immune function, whole blood cytokine levels and the number of peripheral regulatory T cells were analyzed prior to ACT and during the follow up. RESULTS: Transferred cells contained numerous less-differentiated T cells greatly represented by CD27+CD45RA+ or CD28+CD45RA+ cell, which accounted for approximately 65% and 70% of the total, respectively. No ACT related severe or unexpected toxicities were observed. The response rate among patients was 22.2% and the disease control rate was 66.7%. CONCLUSIONS: The results obtained in this phase I trial, indicate that FN-CH296 stimulated T cell therapy was very well tolerated with a level of efficacy that is quite promising. We also surmise that expanding T cell using CH296 is a method that can be applied to other T- cell-based therapies. TRIAL REGISTRATION: UMIN UMIN000001835 Public Library of Science 2014-01-31 /pmc/articles/PMC3908868/ /pubmed/24497917 http://dx.doi.org/10.1371/journal.pone.0083786 Text en © 2014 Ishikawa et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Ishikawa, Takeshi Kokura, Satoshi Enoki, Tatsuji Sakamoto, Naoyuki Okayama, Tetsuya Ideno, Mitsuko Mineno, Junichi Uno, Kazuko Yoshida, Naohisa Kamada, Kazuhiro Katada, Kazuhiro Uchiyama, Kazuhiko Handa, Osamu Takagi, Tomohisa Konishi, Hideyuki Yagi, Nobuaki Naito, Yuji Itoh, Yoshito Yoshikawa, Toshikazu Phase I Clinical Trial of Fibronectin CH296-Stimulated T Cell Therapy in Patients with Advanced Cancer |
title | Phase I Clinical Trial of Fibronectin CH296-Stimulated T Cell Therapy in Patients with Advanced Cancer |
title_full | Phase I Clinical Trial of Fibronectin CH296-Stimulated T Cell Therapy in Patients with Advanced Cancer |
title_fullStr | Phase I Clinical Trial of Fibronectin CH296-Stimulated T Cell Therapy in Patients with Advanced Cancer |
title_full_unstemmed | Phase I Clinical Trial of Fibronectin CH296-Stimulated T Cell Therapy in Patients with Advanced Cancer |
title_short | Phase I Clinical Trial of Fibronectin CH296-Stimulated T Cell Therapy in Patients with Advanced Cancer |
title_sort | phase i clinical trial of fibronectin ch296-stimulated t cell therapy in patients with advanced cancer |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3908868/ https://www.ncbi.nlm.nih.gov/pubmed/24497917 http://dx.doi.org/10.1371/journal.pone.0083786 |
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