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CAR-Modified Vγ9Vδ2 T Cells Propagated Using a Novel Bisphosphonate Prodrug for Allogeneic Adoptive Immunotherapy
The benefits of CAR-T therapy could be expanded to the treatment of solid tumors through the use of derived autologous αβ T cell, but clinical trials of CAR-T therapy for patients with solid tumors have so far been disappointing. CAR-T therapy also faces hurdles due to the time and cost intensive pr...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10341429/ https://www.ncbi.nlm.nih.gov/pubmed/37446055 http://dx.doi.org/10.3390/ijms241310873 |
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author | Wang, Yizheng Wang, Linan Seo, Naohiro Okumura, Satoshi Hayashi, Tae Akahori, Yasushi Fujiwara, Hiroshi Amaishi, Yasunori Okamoto, Sachiko Mineno, Junichi Tanaka, Yoshimasa Kato, Takuma Shiku, Hiroshi |
author_facet | Wang, Yizheng Wang, Linan Seo, Naohiro Okumura, Satoshi Hayashi, Tae Akahori, Yasushi Fujiwara, Hiroshi Amaishi, Yasunori Okamoto, Sachiko Mineno, Junichi Tanaka, Yoshimasa Kato, Takuma Shiku, Hiroshi |
author_sort | Wang, Yizheng |
collection | PubMed |
description | The benefits of CAR-T therapy could be expanded to the treatment of solid tumors through the use of derived autologous αβ T cell, but clinical trials of CAR-T therapy for patients with solid tumors have so far been disappointing. CAR-T therapy also faces hurdles due to the time and cost intensive preparation of CAR-T cell products derived from patients as such CAR-T cells are often poor in quality and low in quantity. These inadequacies may be mitigated through the use of third-party donor derived CAR-T cell products which have a potent anti-tumor function but a constrained GVHD property. Vγ9Vδ2 TCR have been shown to exhibit potent antitumor activity but not alloreactivity. Therefore, in this study, CAR-T cells were prepared from Vγ9Vδ2 T (CAR-γδ T) cells which were expanded by using a novel prodrug PTA. CAR-γδ T cells suppressed tumor growth in an antigen specific manner but only during a limited time window. Provision of GITR co-stimulation enhanced anti-tumor function of CAR-γδ T cells. Our present results indicate that, while further optimization of CAR-γδ T cells is necessary, the present results demonstrate that Vγ9Vδ2 T cells are potential source of ‘off-the-shelf’ CAR-T cell products for successful allogeneic adoptive immunotherapy. |
format | Online Article Text |
id | pubmed-10341429 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-103414292023-07-14 CAR-Modified Vγ9Vδ2 T Cells Propagated Using a Novel Bisphosphonate Prodrug for Allogeneic Adoptive Immunotherapy Wang, Yizheng Wang, Linan Seo, Naohiro Okumura, Satoshi Hayashi, Tae Akahori, Yasushi Fujiwara, Hiroshi Amaishi, Yasunori Okamoto, Sachiko Mineno, Junichi Tanaka, Yoshimasa Kato, Takuma Shiku, Hiroshi Int J Mol Sci Article The benefits of CAR-T therapy could be expanded to the treatment of solid tumors through the use of derived autologous αβ T cell, but clinical trials of CAR-T therapy for patients with solid tumors have so far been disappointing. CAR-T therapy also faces hurdles due to the time and cost intensive preparation of CAR-T cell products derived from patients as such CAR-T cells are often poor in quality and low in quantity. These inadequacies may be mitigated through the use of third-party donor derived CAR-T cell products which have a potent anti-tumor function but a constrained GVHD property. Vγ9Vδ2 TCR have been shown to exhibit potent antitumor activity but not alloreactivity. Therefore, in this study, CAR-T cells were prepared from Vγ9Vδ2 T (CAR-γδ T) cells which were expanded by using a novel prodrug PTA. CAR-γδ T cells suppressed tumor growth in an antigen specific manner but only during a limited time window. Provision of GITR co-stimulation enhanced anti-tumor function of CAR-γδ T cells. Our present results indicate that, while further optimization of CAR-γδ T cells is necessary, the present results demonstrate that Vγ9Vδ2 T cells are potential source of ‘off-the-shelf’ CAR-T cell products for successful allogeneic adoptive immunotherapy. MDPI 2023-06-29 /pmc/articles/PMC10341429/ /pubmed/37446055 http://dx.doi.org/10.3390/ijms241310873 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Wang, Yizheng Wang, Linan Seo, Naohiro Okumura, Satoshi Hayashi, Tae Akahori, Yasushi Fujiwara, Hiroshi Amaishi, Yasunori Okamoto, Sachiko Mineno, Junichi Tanaka, Yoshimasa Kato, Takuma Shiku, Hiroshi CAR-Modified Vγ9Vδ2 T Cells Propagated Using a Novel Bisphosphonate Prodrug for Allogeneic Adoptive Immunotherapy |
title | CAR-Modified Vγ9Vδ2 T Cells Propagated Using a Novel Bisphosphonate Prodrug for Allogeneic Adoptive Immunotherapy |
title_full | CAR-Modified Vγ9Vδ2 T Cells Propagated Using a Novel Bisphosphonate Prodrug for Allogeneic Adoptive Immunotherapy |
title_fullStr | CAR-Modified Vγ9Vδ2 T Cells Propagated Using a Novel Bisphosphonate Prodrug for Allogeneic Adoptive Immunotherapy |
title_full_unstemmed | CAR-Modified Vγ9Vδ2 T Cells Propagated Using a Novel Bisphosphonate Prodrug for Allogeneic Adoptive Immunotherapy |
title_short | CAR-Modified Vγ9Vδ2 T Cells Propagated Using a Novel Bisphosphonate Prodrug for Allogeneic Adoptive Immunotherapy |
title_sort | car-modified vγ9vδ2 t cells propagated using a novel bisphosphonate prodrug for allogeneic adoptive immunotherapy |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10341429/ https://www.ncbi.nlm.nih.gov/pubmed/37446055 http://dx.doi.org/10.3390/ijms241310873 |
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