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A Comparative Study of Replication-Incompetent and -Competent Adenoviral Therapy-Mediated Immune Response in a Murine Glioma Model
Oncolytic virotherapy is a treatment approach with increasing clinical relevance, as indicated by the marked survival benefit seen in animal models and its current exploration in human patients with cancer. The use of an adenovirus vector for this therapeutic modality is common, has significant clin...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society of Gene & Cell Therapy
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5443908/ https://www.ncbi.nlm.nih.gov/pubmed/28573184 http://dx.doi.org/10.1016/j.omto.2017.05.001 |
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author | Kim, Julius W. Miska, Jason Young, Jacob S. Rashidi, Aida Kane, J. Robert Panek, Wojciech K. Kanojia, Deepak Han, Yu Balyasnikova, Irina V. Lesniak, Maciej S. |
author_facet | Kim, Julius W. Miska, Jason Young, Jacob S. Rashidi, Aida Kane, J. Robert Panek, Wojciech K. Kanojia, Deepak Han, Yu Balyasnikova, Irina V. Lesniak, Maciej S. |
author_sort | Kim, Julius W. |
collection | PubMed |
description | Oncolytic virotherapy is a treatment approach with increasing clinical relevance, as indicated by the marked survival benefit seen in animal models and its current exploration in human patients with cancer. The use of an adenovirus vector for this therapeutic modality is common, has significant clinical benefit in animals, and its efficacy has recently been linked to an anti-tumor immune response that occurs following tumor antigen presentation. Here, we analyzed the adaptive immune system’s response following viral infection by comparing replication-incompetent and replication-competent adenoviral vectors. Our findings suggest that cell death caused by replication-competent adenoviral vectors is required to induce a significant anti-tumor immune response and survival benefits in immunocompetent mice bearing intracranial glioma. We observed significant changes in the repertoire of immune cells in the brain and draining lymph nodes and significant recruitment of CD103+ dendritic cells (DCs) in response to oncolytic adenoviral therapy, suggesting the active role of the immune system in anti-tumor response. Our data suggest that the response to oncolytic virotherapy is accompanied by local and systemic immune responses and should be taken in consideration in the future design of the clinical studies evaluating oncolytic virotherapy in patients with glioblastoma multiforme (GBM). |
format | Online Article Text |
id | pubmed-5443908 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | American Society of Gene & Cell Therapy |
record_format | MEDLINE/PubMed |
spelling | pubmed-54439082017-06-01 A Comparative Study of Replication-Incompetent and -Competent Adenoviral Therapy-Mediated Immune Response in a Murine Glioma Model Kim, Julius W. Miska, Jason Young, Jacob S. Rashidi, Aida Kane, J. Robert Panek, Wojciech K. Kanojia, Deepak Han, Yu Balyasnikova, Irina V. Lesniak, Maciej S. Mol Ther Oncolytics Original Article Oncolytic virotherapy is a treatment approach with increasing clinical relevance, as indicated by the marked survival benefit seen in animal models and its current exploration in human patients with cancer. The use of an adenovirus vector for this therapeutic modality is common, has significant clinical benefit in animals, and its efficacy has recently been linked to an anti-tumor immune response that occurs following tumor antigen presentation. Here, we analyzed the adaptive immune system’s response following viral infection by comparing replication-incompetent and replication-competent adenoviral vectors. Our findings suggest that cell death caused by replication-competent adenoviral vectors is required to induce a significant anti-tumor immune response and survival benefits in immunocompetent mice bearing intracranial glioma. We observed significant changes in the repertoire of immune cells in the brain and draining lymph nodes and significant recruitment of CD103+ dendritic cells (DCs) in response to oncolytic adenoviral therapy, suggesting the active role of the immune system in anti-tumor response. Our data suggest that the response to oncolytic virotherapy is accompanied by local and systemic immune responses and should be taken in consideration in the future design of the clinical studies evaluating oncolytic virotherapy in patients with glioblastoma multiforme (GBM). American Society of Gene & Cell Therapy 2017-05-06 /pmc/articles/PMC5443908/ /pubmed/28573184 http://dx.doi.org/10.1016/j.omto.2017.05.001 Text en © 2017 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Original Article Kim, Julius W. Miska, Jason Young, Jacob S. Rashidi, Aida Kane, J. Robert Panek, Wojciech K. Kanojia, Deepak Han, Yu Balyasnikova, Irina V. Lesniak, Maciej S. A Comparative Study of Replication-Incompetent and -Competent Adenoviral Therapy-Mediated Immune Response in a Murine Glioma Model |
title | A Comparative Study of Replication-Incompetent and -Competent Adenoviral Therapy-Mediated Immune Response in a Murine Glioma Model |
title_full | A Comparative Study of Replication-Incompetent and -Competent Adenoviral Therapy-Mediated Immune Response in a Murine Glioma Model |
title_fullStr | A Comparative Study of Replication-Incompetent and -Competent Adenoviral Therapy-Mediated Immune Response in a Murine Glioma Model |
title_full_unstemmed | A Comparative Study of Replication-Incompetent and -Competent Adenoviral Therapy-Mediated Immune Response in a Murine Glioma Model |
title_short | A Comparative Study of Replication-Incompetent and -Competent Adenoviral Therapy-Mediated Immune Response in a Murine Glioma Model |
title_sort | comparative study of replication-incompetent and -competent adenoviral therapy-mediated immune response in a murine glioma model |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5443908/ https://www.ncbi.nlm.nih.gov/pubmed/28573184 http://dx.doi.org/10.1016/j.omto.2017.05.001 |
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