Retargeted and Multi-cytokine-Armed Herpes Virus Is a Potent Cancer Endovaccine for Local and Systemic Anti-tumor Treatment
Oncolytic viruses (OVs) are novel anti-tumor agents with the ability to selectively infect and kill tumor cells while sparing normal tissue. Beyond tumor cytolysis, OVs are capable of priming an anti-tumor immune response via lysis and cross-presentation of locally expressed endogenous tumor antigen...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society of Gene & Cell Therapy
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7658578/ https://www.ncbi.nlm.nih.gov/pubmed/33209980 http://dx.doi.org/10.1016/j.omto.2020.10.006 |
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author | De Lucia, Maria Cotugno, Gabriella Bignone, Veronica Garzia, Irene Nocchi, Linda Langone, Francesca Petrovic, Biljana Sasso, Emanuele Pepe, Simona Froechlich, Guendalina Gentile, Chiara Zambrano, Nicola Campadelli-Fiume, Gabriella Nicosia, Alfredo Scarselli, Elisa D’Alise, Anna Morena |
author_facet | De Lucia, Maria Cotugno, Gabriella Bignone, Veronica Garzia, Irene Nocchi, Linda Langone, Francesca Petrovic, Biljana Sasso, Emanuele Pepe, Simona Froechlich, Guendalina Gentile, Chiara Zambrano, Nicola Campadelli-Fiume, Gabriella Nicosia, Alfredo Scarselli, Elisa D’Alise, Anna Morena |
author_sort | De Lucia, Maria |
collection | PubMed |
description | Oncolytic viruses (OVs) are novel anti-tumor agents with the ability to selectively infect and kill tumor cells while sparing normal tissue. Beyond tumor cytolysis, OVs are capable of priming an anti-tumor immune response via lysis and cross-presentation of locally expressed endogenous tumor antigens, acting as an “endovaccine.” The effectiveness of OVs, similar to other immunotherapies, can be hampered by an immunosuppressive tumor microenvironment. In this study, we modified a previously generated oncolytic herpes simplex virus (oHSV) retargeted to the human HER2 (hHER2) tumor molecule and encoding murine interleukin-12 (mIL-12), by insertion of a second immunomodulatory molecule, murine granulocyte-macrophage colony-stimulating factor (mGM-CSF), to maximize therapeutic efficacy. We assessed the efficacy of this double-armed virus (R-123) compared to singly expressing GM-CSF and IL-12 oHSVs in tumor-bearing mice. While monotherapies were poorly effective, combination with α-PD1 enhanced the anti-tumor response, with the highest efficacy of 100% response rate achieved by the combination of R-123 and α-PD1. Efficacy was T cell-dependent, and the induced immunity was long lasting and able to reject a second contralateral tumor. Importantly, systemic delivery of R-123 combined with α-PD1 was effective in inhibiting the development of tumor metastasis. As such, this approach could have a significant therapeutic impact paving the way for further development of this platform in cancer immunotherapy. |
format | Online Article Text |
id | pubmed-7658578 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | American Society of Gene & Cell Therapy |
record_format | MEDLINE/PubMed |
spelling | pubmed-76585782020-11-17 Retargeted and Multi-cytokine-Armed Herpes Virus Is a Potent Cancer Endovaccine for Local and Systemic Anti-tumor Treatment De Lucia, Maria Cotugno, Gabriella Bignone, Veronica Garzia, Irene Nocchi, Linda Langone, Francesca Petrovic, Biljana Sasso, Emanuele Pepe, Simona Froechlich, Guendalina Gentile, Chiara Zambrano, Nicola Campadelli-Fiume, Gabriella Nicosia, Alfredo Scarselli, Elisa D’Alise, Anna Morena Mol Ther Oncolytics Original Article Oncolytic viruses (OVs) are novel anti-tumor agents with the ability to selectively infect and kill tumor cells while sparing normal tissue. Beyond tumor cytolysis, OVs are capable of priming an anti-tumor immune response via lysis and cross-presentation of locally expressed endogenous tumor antigens, acting as an “endovaccine.” The effectiveness of OVs, similar to other immunotherapies, can be hampered by an immunosuppressive tumor microenvironment. In this study, we modified a previously generated oncolytic herpes simplex virus (oHSV) retargeted to the human HER2 (hHER2) tumor molecule and encoding murine interleukin-12 (mIL-12), by insertion of a second immunomodulatory molecule, murine granulocyte-macrophage colony-stimulating factor (mGM-CSF), to maximize therapeutic efficacy. We assessed the efficacy of this double-armed virus (R-123) compared to singly expressing GM-CSF and IL-12 oHSVs in tumor-bearing mice. While monotherapies were poorly effective, combination with α-PD1 enhanced the anti-tumor response, with the highest efficacy of 100% response rate achieved by the combination of R-123 and α-PD1. Efficacy was T cell-dependent, and the induced immunity was long lasting and able to reject a second contralateral tumor. Importantly, systemic delivery of R-123 combined with α-PD1 was effective in inhibiting the development of tumor metastasis. As such, this approach could have a significant therapeutic impact paving the way for further development of this platform in cancer immunotherapy. American Society of Gene & Cell Therapy 2020-10-14 /pmc/articles/PMC7658578/ /pubmed/33209980 http://dx.doi.org/10.1016/j.omto.2020.10.006 Text en © 2020 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 De Lucia, Maria Cotugno, Gabriella Bignone, Veronica Garzia, Irene Nocchi, Linda Langone, Francesca Petrovic, Biljana Sasso, Emanuele Pepe, Simona Froechlich, Guendalina Gentile, Chiara Zambrano, Nicola Campadelli-Fiume, Gabriella Nicosia, Alfredo Scarselli, Elisa D’Alise, Anna Morena Retargeted and Multi-cytokine-Armed Herpes Virus Is a Potent Cancer Endovaccine for Local and Systemic Anti-tumor Treatment |
title | Retargeted and Multi-cytokine-Armed Herpes Virus Is a Potent Cancer Endovaccine for Local and Systemic Anti-tumor Treatment |
title_full | Retargeted and Multi-cytokine-Armed Herpes Virus Is a Potent Cancer Endovaccine for Local and Systemic Anti-tumor Treatment |
title_fullStr | Retargeted and Multi-cytokine-Armed Herpes Virus Is a Potent Cancer Endovaccine for Local and Systemic Anti-tumor Treatment |
title_full_unstemmed | Retargeted and Multi-cytokine-Armed Herpes Virus Is a Potent Cancer Endovaccine for Local and Systemic Anti-tumor Treatment |
title_short | Retargeted and Multi-cytokine-Armed Herpes Virus Is a Potent Cancer Endovaccine for Local and Systemic Anti-tumor Treatment |
title_sort | retargeted and multi-cytokine-armed herpes virus is a potent cancer endovaccine for local and systemic anti-tumor treatment |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7658578/ https://www.ncbi.nlm.nih.gov/pubmed/33209980 http://dx.doi.org/10.1016/j.omto.2020.10.006 |
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