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Prophylactic and therapeutic adenoviral vector-based multivirus-specific T-cell immunotherapy for transplant patients

Viral infections including cytomegalovirus, Epstein-Barr virus, adenovirus, and BK virus are a common and predictable problem in transplant recipients. While cellular immune therapies have been successfully used to tackle infectious complications in transplant recipients, manufacturing immunotherapi...

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Autores principales: Dasari, Vijayendra, Schuessler, Andrea, Smith, Corey, Wong, Yide, Miles, John J, Smyth, Mark J, Ambalathingal, George, Francis, Ross, Campbell, Scott, Chambers, Daniel, Khanna, Rajiv
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4997746/
https://www.ncbi.nlm.nih.gov/pubmed/27606351
http://dx.doi.org/10.1038/mtm.2016.58
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author Dasari, Vijayendra
Schuessler, Andrea
Smith, Corey
Wong, Yide
Miles, John J
Smyth, Mark J
Ambalathingal, George
Francis, Ross
Campbell, Scott
Chambers, Daniel
Khanna, Rajiv
author_facet Dasari, Vijayendra
Schuessler, Andrea
Smith, Corey
Wong, Yide
Miles, John J
Smyth, Mark J
Ambalathingal, George
Francis, Ross
Campbell, Scott
Chambers, Daniel
Khanna, Rajiv
author_sort Dasari, Vijayendra
collection PubMed
description Viral infections including cytomegalovirus, Epstein-Barr virus, adenovirus, and BK virus are a common and predictable problem in transplant recipients. While cellular immune therapies have been successfully used to tackle infectious complications in transplant recipients, manufacturing immunotherapies to address the multitude of possible pathogens can be technically challenging and labor-intensive. Here we describe a novel adenoviral antigen presentation platform (Ad-MvP) as a tool for rapid generation of multivirus-specific T-cells in a single step. Ad-MvP encodes 32 CD8+ T-cell epitopes from cytomegalovirus, Epstein-Barr virus, adenovirus, and BK virus as a contiguous polyepitope. We demonstrate that Ad-MvP vector can be successfully used for rapid in vitro expansion of multivirus-specific T-cells from transplant recipients and in vivo priming of antiviral T-cell immunity. Most importantly, using an in vivo murine model of Epstein-Barr virus-induced lymphoma, we also show that adoptive immunotherapy with Ad-MvP expanded autologous and allogeneic multivirus-specific T-cells is highly effective in controlling Epstein-Barr virus tumor outgrowth and improving overall survival. We propose that Ad-MvP has wide ranging therapeutic applications in greatly facilitating in vivo priming of antiviral T-cells, the generation of third-party T-cell banks as “off-the-shelf” therapeutics as well as autologous T-cell therapies for transplant patients.
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spelling pubmed-49977462016-09-07 Prophylactic and therapeutic adenoviral vector-based multivirus-specific T-cell immunotherapy for transplant patients Dasari, Vijayendra Schuessler, Andrea Smith, Corey Wong, Yide Miles, John J Smyth, Mark J Ambalathingal, George Francis, Ross Campbell, Scott Chambers, Daniel Khanna, Rajiv Mol Ther Methods Clin Dev Article Viral infections including cytomegalovirus, Epstein-Barr virus, adenovirus, and BK virus are a common and predictable problem in transplant recipients. While cellular immune therapies have been successfully used to tackle infectious complications in transplant recipients, manufacturing immunotherapies to address the multitude of possible pathogens can be technically challenging and labor-intensive. Here we describe a novel adenoviral antigen presentation platform (Ad-MvP) as a tool for rapid generation of multivirus-specific T-cells in a single step. Ad-MvP encodes 32 CD8+ T-cell epitopes from cytomegalovirus, Epstein-Barr virus, adenovirus, and BK virus as a contiguous polyepitope. We demonstrate that Ad-MvP vector can be successfully used for rapid in vitro expansion of multivirus-specific T-cells from transplant recipients and in vivo priming of antiviral T-cell immunity. Most importantly, using an in vivo murine model of Epstein-Barr virus-induced lymphoma, we also show that adoptive immunotherapy with Ad-MvP expanded autologous and allogeneic multivirus-specific T-cells is highly effective in controlling Epstein-Barr virus tumor outgrowth and improving overall survival. We propose that Ad-MvP has wide ranging therapeutic applications in greatly facilitating in vivo priming of antiviral T-cells, the generation of third-party T-cell banks as “off-the-shelf” therapeutics as well as autologous T-cell therapies for transplant patients. Nature Publishing Group 2016-08-24 /pmc/articles/PMC4997746/ /pubmed/27606351 http://dx.doi.org/10.1038/mtm.2016.58 Text en Copyright © 2016 Official journal of the American Society of Gene & Cell Therapy http://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/
spellingShingle Article
Dasari, Vijayendra
Schuessler, Andrea
Smith, Corey
Wong, Yide
Miles, John J
Smyth, Mark J
Ambalathingal, George
Francis, Ross
Campbell, Scott
Chambers, Daniel
Khanna, Rajiv
Prophylactic and therapeutic adenoviral vector-based multivirus-specific T-cell immunotherapy for transplant patients
title Prophylactic and therapeutic adenoviral vector-based multivirus-specific T-cell immunotherapy for transplant patients
title_full Prophylactic and therapeutic adenoviral vector-based multivirus-specific T-cell immunotherapy for transplant patients
title_fullStr Prophylactic and therapeutic adenoviral vector-based multivirus-specific T-cell immunotherapy for transplant patients
title_full_unstemmed Prophylactic and therapeutic adenoviral vector-based multivirus-specific T-cell immunotherapy for transplant patients
title_short Prophylactic and therapeutic adenoviral vector-based multivirus-specific T-cell immunotherapy for transplant patients
title_sort prophylactic and therapeutic adenoviral vector-based multivirus-specific t-cell immunotherapy for transplant patients
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4997746/
https://www.ncbi.nlm.nih.gov/pubmed/27606351
http://dx.doi.org/10.1038/mtm.2016.58
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