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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doaj-01fc9b719cc148b897cb643e8683781e2020-11-25T01:59:45ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0191e8378610.1371/journal.pone.0083786Phase I clinical trial of fibronectin CH296-stimulated T cell therapy in patients with advanced cancer.Takeshi IshikawaSatoshi KokuraTatsuji EnokiNaoyuki SakamotoTetsuya OkayamaMitsuko IdenoJunichi MinenoKazuko UnoNaohisa YoshidaKazuhiro KamadaKazuhiro KatadaKazuhiko UchiyamaOsamu HandaTomohisa TakagiHideyuki KonishiNobuaki YagiYuji NaitoYoshito ItohToshikazu YoshikawaBACKGROUND: 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.http://europepmc.org/articles/PMC3908868?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Takeshi Ishikawa Satoshi Kokura Tatsuji Enoki Naoyuki Sakamoto Tetsuya Okayama Mitsuko Ideno Junichi Mineno Kazuko Uno Naohisa Yoshida Kazuhiro Kamada Kazuhiro Katada Kazuhiko Uchiyama Osamu Handa Tomohisa Takagi Hideyuki Konishi Nobuaki Yagi Yuji Naito Yoshito Itoh Toshikazu Yoshikawa |
spellingShingle |
Takeshi Ishikawa Satoshi Kokura Tatsuji Enoki Naoyuki Sakamoto Tetsuya Okayama Mitsuko Ideno Junichi Mineno Kazuko Uno Naohisa Yoshida Kazuhiro Kamada Kazuhiro Katada Kazuhiko Uchiyama Osamu Handa Tomohisa Takagi Hideyuki Konishi Nobuaki Yagi Yuji Naito Yoshito Itoh Toshikazu Yoshikawa Phase I clinical trial of fibronectin CH296-stimulated T cell therapy in patients with advanced cancer. PLoS ONE |
author_facet |
Takeshi Ishikawa Satoshi Kokura Tatsuji Enoki Naoyuki Sakamoto Tetsuya Okayama Mitsuko Ideno Junichi Mineno Kazuko Uno Naohisa Yoshida Kazuhiro Kamada Kazuhiro Katada Kazuhiko Uchiyama Osamu Handa Tomohisa Takagi Hideyuki Konishi Nobuaki Yagi Yuji Naito Yoshito Itoh Toshikazu Yoshikawa |
author_sort |
Takeshi Ishikawa |
title |
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_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_sort |
phase i clinical trial of fibronectin ch296-stimulated t cell therapy in patients with advanced cancer. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2014-01-01 |
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. |
url |
http://europepmc.org/articles/PMC3908868?pdf=render |
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