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Immunological Effects and Viral Gene Expression Determine the Efficacy of Oncolytic Measles Vaccines Encoding IL-12 or IL-15 Agonists
Tumor-targeted immunomodulation using oncolytic viral vectors is currently being investigated as a promising strategy in cancer therapy. In a previous study, we showed that a measles virus Schwarz vaccine strain (MeVac) vector encoding an interleukin-12 fusion protein (FmIL-12) is an effective immun...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6832518/ https://www.ncbi.nlm.nih.gov/pubmed/31623390 http://dx.doi.org/10.3390/v11100914 |
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author | Backhaus, Paul S. Veinalde, Rūta Hartmann, Laura Dunder, Jessica E. Jeworowski, Lara M. Albert, Jessica Hoyler, Birgit Poth, Tanja Jäger, Dirk Ungerechts, Guy Engeland, Christine E. |
author_facet | Backhaus, Paul S. Veinalde, Rūta Hartmann, Laura Dunder, Jessica E. Jeworowski, Lara M. Albert, Jessica Hoyler, Birgit Poth, Tanja Jäger, Dirk Ungerechts, Guy Engeland, Christine E. |
author_sort | Backhaus, Paul S. |
collection | PubMed |
description | Tumor-targeted immunomodulation using oncolytic viral vectors is currently being investigated as a promising strategy in cancer therapy. In a previous study, we showed that a measles virus Schwarz vaccine strain (MeVac) vector encoding an interleukin-12 fusion protein (FmIL-12) is an effective immunotherapy in the MC38cea murine colon adenocarcinoma model. We hypothesized that MeVac encoding interleukin-15 may mediate enhanced T and NK cell responses and thus increase the therapeutic efficacy, especially in NK cell-controlled tumors. Therefore, we generated MeVac vectors encoding an interleukin-15 superagonist, FmIL-15. Replication and oncolytic capacity, transgene expression, and functionality of MeVac FmIL-15 vectors were validated in vitro. Effects on the tumor immune landscape and therapeutic efficacy of both FmIL-12 and FmIL-15 vectors were studied in the MC38cea and B16hCD46 tumor models. Treatment with MeVac FmIL-15 increased T and NK cell infiltration in both models. However, MeVac FmIL-12 showed more robust viral gene expression and immune activation, resulting in superior anti-tumor efficacy. Based on these results, MeVac encoding a human IL-12 fusion protein was developed for future clinical translation. |
format | Online Article Text |
id | pubmed-6832518 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-68325182019-11-25 Immunological Effects and Viral Gene Expression Determine the Efficacy of Oncolytic Measles Vaccines Encoding IL-12 or IL-15 Agonists Backhaus, Paul S. Veinalde, Rūta Hartmann, Laura Dunder, Jessica E. Jeworowski, Lara M. Albert, Jessica Hoyler, Birgit Poth, Tanja Jäger, Dirk Ungerechts, Guy Engeland, Christine E. Viruses Article Tumor-targeted immunomodulation using oncolytic viral vectors is currently being investigated as a promising strategy in cancer therapy. In a previous study, we showed that a measles virus Schwarz vaccine strain (MeVac) vector encoding an interleukin-12 fusion protein (FmIL-12) is an effective immunotherapy in the MC38cea murine colon adenocarcinoma model. We hypothesized that MeVac encoding interleukin-15 may mediate enhanced T and NK cell responses and thus increase the therapeutic efficacy, especially in NK cell-controlled tumors. Therefore, we generated MeVac vectors encoding an interleukin-15 superagonist, FmIL-15. Replication and oncolytic capacity, transgene expression, and functionality of MeVac FmIL-15 vectors were validated in vitro. Effects on the tumor immune landscape and therapeutic efficacy of both FmIL-12 and FmIL-15 vectors were studied in the MC38cea and B16hCD46 tumor models. Treatment with MeVac FmIL-15 increased T and NK cell infiltration in both models. However, MeVac FmIL-12 showed more robust viral gene expression and immune activation, resulting in superior anti-tumor efficacy. Based on these results, MeVac encoding a human IL-12 fusion protein was developed for future clinical translation. MDPI 2019-10-03 /pmc/articles/PMC6832518/ /pubmed/31623390 http://dx.doi.org/10.3390/v11100914 Text en © 2019 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Backhaus, Paul S. Veinalde, Rūta Hartmann, Laura Dunder, Jessica E. Jeworowski, Lara M. Albert, Jessica Hoyler, Birgit Poth, Tanja Jäger, Dirk Ungerechts, Guy Engeland, Christine E. Immunological Effects and Viral Gene Expression Determine the Efficacy of Oncolytic Measles Vaccines Encoding IL-12 or IL-15 Agonists |
title | Immunological Effects and Viral Gene Expression Determine the Efficacy of Oncolytic Measles Vaccines Encoding IL-12 or IL-15 Agonists |
title_full | Immunological Effects and Viral Gene Expression Determine the Efficacy of Oncolytic Measles Vaccines Encoding IL-12 or IL-15 Agonists |
title_fullStr | Immunological Effects and Viral Gene Expression Determine the Efficacy of Oncolytic Measles Vaccines Encoding IL-12 or IL-15 Agonists |
title_full_unstemmed | Immunological Effects and Viral Gene Expression Determine the Efficacy of Oncolytic Measles Vaccines Encoding IL-12 or IL-15 Agonists |
title_short | Immunological Effects and Viral Gene Expression Determine the Efficacy of Oncolytic Measles Vaccines Encoding IL-12 or IL-15 Agonists |
title_sort | immunological effects and viral gene expression determine the efficacy of oncolytic measles vaccines encoding il-12 or il-15 agonists |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6832518/ https://www.ncbi.nlm.nih.gov/pubmed/31623390 http://dx.doi.org/10.3390/v11100914 |
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