Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Russell, Luke, Peng, Kah Whye, Russell, Stephen J., Diaz, Rosa Maria
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2019
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
_version_ 1783458777815580672
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
work_keys_str_mv AT russellluke oncolyticvirusesprimingtimeforcancerimmunotherapy
AT pengkahwhye oncolyticvirusesprimingtimeforcancerimmunotherapy
AT russellstephenj oncolyticvirusesprimingtimeforcancerimmunotherapy
AT diazrosamaria oncolyticvirusesprimingtimeforcancerimmunotherapy