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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
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
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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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