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Oncolytic Viruses: Priming Time for Cancer Immunotherapy
New immuno-oncology therapies are improving cancer treatments beyond the former standard of care, as evidenced by the recent and continuing clinical approvals for immunotherapies in a broad range of indications. However, a majority of patients (particularly those with immunologically cold tumors) st...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer International Publishing
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6790338/ https://www.ncbi.nlm.nih.gov/pubmed/31321623 http://dx.doi.org/10.1007/s40259-019-00367-0 |
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author | Russell, Luke Peng, Kah Whye Russell, Stephen J. Diaz, Rosa Maria |
author_facet | Russell, Luke Peng, Kah Whye Russell, Stephen J. Diaz, Rosa Maria |
author_sort | Russell, Luke |
collection | PubMed |
description | New immuno-oncology therapies are improving cancer treatments beyond the former standard of care, as evidenced by the recent and continuing clinical approvals for immunotherapies in a broad range of indications. However, a majority of patients (particularly those with immunologically cold tumors) still do not benefit, highlighting the need for rational combination approaches. Oncolytic viruses (OV) both directly kill tumor cells and inflame the tumor microenvironment. While OV spread can be limited by the generation of antiviral immune responses, the initial local tumor cell killing can reverse the immunosuppressive tumor microenvironment, resulting in more effective release of tumor-associated antigens (TAAs), cross-presentation, and antitumoral effector T cell recruitment. Moreover, many OVs can be engineered to express immunomodulatory genes. Rational combination approaches to cancer immunotherapy include the use of OVs in combination with immune checkpoint inhibitors (ICIs) or adoptive T cell therapy (ACT) to promote sustained antitumoral immune responses. OV combinations have additive or synergistic efficacy in preclinical tumor models with ICIs or ACT. Several preclinical studies have confirmed systemic reactivation and proliferation of adoptively transferred antitumoral T cells in conjunction with oncolytic OVs (expressing cytokines or TAAs) resulting from the specific tumor cell killing and immunostimulation of the tumor microenvironment which leads to increased tumor trafficking, activity, and survival. Recent clinical trials combining OVs with ICIs have shown additive effects in melanoma. Additional clinical data in an expanded range of patient indications are eagerly awaited. The relative timings of OV and ICI combination remains under-studied and is an area for continued exploration. Studies systematically exploring the effects of systemic ICIs prior to, concomitantly with, or following OV therapy will aid in the future design of clinical trials to enhance efficacy and increase patient response rates. |
format | Online Article Text |
id | pubmed-6790338 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Springer International Publishing |
record_format | MEDLINE/PubMed |
spelling | pubmed-67903382019-10-17 Oncolytic Viruses: Priming Time for Cancer Immunotherapy Russell, Luke Peng, Kah Whye Russell, Stephen J. Diaz, Rosa Maria BioDrugs Review Article New immuno-oncology therapies are improving cancer treatments beyond the former standard of care, as evidenced by the recent and continuing clinical approvals for immunotherapies in a broad range of indications. However, a majority of patients (particularly those with immunologically cold tumors) still do not benefit, highlighting the need for rational combination approaches. Oncolytic viruses (OV) both directly kill tumor cells and inflame the tumor microenvironment. While OV spread can be limited by the generation of antiviral immune responses, the initial local tumor cell killing can reverse the immunosuppressive tumor microenvironment, resulting in more effective release of tumor-associated antigens (TAAs), cross-presentation, and antitumoral effector T cell recruitment. Moreover, many OVs can be engineered to express immunomodulatory genes. Rational combination approaches to cancer immunotherapy include the use of OVs in combination with immune checkpoint inhibitors (ICIs) or adoptive T cell therapy (ACT) to promote sustained antitumoral immune responses. OV combinations have additive or synergistic efficacy in preclinical tumor models with ICIs or ACT. Several preclinical studies have confirmed systemic reactivation and proliferation of adoptively transferred antitumoral T cells in conjunction with oncolytic OVs (expressing cytokines or TAAs) resulting from the specific tumor cell killing and immunostimulation of the tumor microenvironment which leads to increased tumor trafficking, activity, and survival. Recent clinical trials combining OVs with ICIs have shown additive effects in melanoma. Additional clinical data in an expanded range of patient indications are eagerly awaited. The relative timings of OV and ICI combination remains under-studied and is an area for continued exploration. Studies systematically exploring the effects of systemic ICIs prior to, concomitantly with, or following OV therapy will aid in the future design of clinical trials to enhance efficacy and increase patient response rates. Springer International Publishing 2019-07-18 2019 /pmc/articles/PMC6790338/ /pubmed/31321623 http://dx.doi.org/10.1007/s40259-019-00367-0 Text en © The Author(s) 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/), which permits any noncommercial use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
spellingShingle | Review Article Russell, Luke Peng, Kah Whye Russell, Stephen J. Diaz, Rosa Maria Oncolytic Viruses: Priming Time for Cancer Immunotherapy |
title | Oncolytic Viruses: Priming Time for Cancer Immunotherapy |
title_full | Oncolytic Viruses: Priming Time for Cancer Immunotherapy |
title_fullStr | Oncolytic Viruses: Priming Time for Cancer Immunotherapy |
title_full_unstemmed | Oncolytic Viruses: Priming Time for Cancer Immunotherapy |
title_short | Oncolytic Viruses: Priming Time for Cancer Immunotherapy |
title_sort | oncolytic viruses: priming time for cancer immunotherapy |
topic | Review Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6790338/ https://www.ncbi.nlm.nih.gov/pubmed/31321623 http://dx.doi.org/10.1007/s40259-019-00367-0 |
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