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Immunomodulatory Arming Factors—The Current Paradigm for Oncolytic Vectors Relies on Immune Stimulating Molecules

The dogma of engineering oncolytic viral vectors has shifted from emphasizing the viral lysis of individual cancer cells to the recruitment and coordination of the adaptive immune system to clear the tumor. To accomplish this, researchers have been adding several classes of transgenes to their prefe...

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Autores principales: Peters, Cole W. D., Nigim, Fares
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8396515/
https://www.ncbi.nlm.nih.gov/pubmed/34445759
http://dx.doi.org/10.3390/ijms22169051
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author Peters, Cole W. D.
Nigim, Fares
author_facet Peters, Cole W. D.
Nigim, Fares
author_sort Peters, Cole W. D.
collection PubMed
description The dogma of engineering oncolytic viral vectors has shifted from emphasizing the viral lysis of individual cancer cells to the recruitment and coordination of the adaptive immune system to clear the tumor. To accomplish this, researchers have been adding several classes of transgenes to their preferred viral platforms. The most prevalent of these include antibodies and targeting moieties, interleukins and cytokines, and genes which rely on small molecule co-administration for tumor killing. Most current vectors rely exclusively on one of these types of transgenes to elicit the desired immune response to clear tumors, but are not mutually exclusive, with several larger OVs armed with several of these factors. The common theme of emerging armed vectors is to simply initiate or enhance infiltration of effector CD8+ T cells to clear the tumor locally at OV infection sites, and systemically throughout the body where the OV has not infected tumor cells. The precision of oncolytic vectors to target a cell type or tissue remains its key advantage over small-molecule drugs. Unlike chemo- and other drug therapies, viral vectors can be made to specifically infect and grow within tumor cells. This ensures localized expression of the therapeutic transgene to the diseased tissue, thereby limiting systemic toxicity. This review will examine the immunomodulating transgenes of current OVs, describe their general effect on the immune system, and provide the rationale for each vector’s use in clearing its targeted tumor.
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spelling pubmed-83965152021-08-28 Immunomodulatory Arming Factors—The Current Paradigm for Oncolytic Vectors Relies on Immune Stimulating Molecules Peters, Cole W. D. Nigim, Fares Int J Mol Sci Review The dogma of engineering oncolytic viral vectors has shifted from emphasizing the viral lysis of individual cancer cells to the recruitment and coordination of the adaptive immune system to clear the tumor. To accomplish this, researchers have been adding several classes of transgenes to their preferred viral platforms. The most prevalent of these include antibodies and targeting moieties, interleukins and cytokines, and genes which rely on small molecule co-administration for tumor killing. Most current vectors rely exclusively on one of these types of transgenes to elicit the desired immune response to clear tumors, but are not mutually exclusive, with several larger OVs armed with several of these factors. The common theme of emerging armed vectors is to simply initiate or enhance infiltration of effector CD8+ T cells to clear the tumor locally at OV infection sites, and systemically throughout the body where the OV has not infected tumor cells. The precision of oncolytic vectors to target a cell type or tissue remains its key advantage over small-molecule drugs. Unlike chemo- and other drug therapies, viral vectors can be made to specifically infect and grow within tumor cells. This ensures localized expression of the therapeutic transgene to the diseased tissue, thereby limiting systemic toxicity. This review will examine the immunomodulating transgenes of current OVs, describe their general effect on the immune system, and provide the rationale for each vector’s use in clearing its targeted tumor. MDPI 2021-08-22 /pmc/articles/PMC8396515/ /pubmed/34445759 http://dx.doi.org/10.3390/ijms22169051 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Peters, Cole W. D.
Nigim, Fares
Immunomodulatory Arming Factors—The Current Paradigm for Oncolytic Vectors Relies on Immune Stimulating Molecules
title Immunomodulatory Arming Factors—The Current Paradigm for Oncolytic Vectors Relies on Immune Stimulating Molecules
title_full Immunomodulatory Arming Factors—The Current Paradigm for Oncolytic Vectors Relies on Immune Stimulating Molecules
title_fullStr Immunomodulatory Arming Factors—The Current Paradigm for Oncolytic Vectors Relies on Immune Stimulating Molecules
title_full_unstemmed Immunomodulatory Arming Factors—The Current Paradigm for Oncolytic Vectors Relies on Immune Stimulating Molecules
title_short Immunomodulatory Arming Factors—The Current Paradigm for Oncolytic Vectors Relies on Immune Stimulating Molecules
title_sort immunomodulatory arming factors—the current paradigm for oncolytic vectors relies on immune stimulating molecules
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8396515/
https://www.ncbi.nlm.nih.gov/pubmed/34445759
http://dx.doi.org/10.3390/ijms22169051
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