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Engineering Cancer Selective Virotherapies: Are the Pieces of the Puzzle Falling into Place?

Advances in gene therapy, synthetic biology, cancer genomics, and patient-derived cancer models have expanded the repertoire of strategies for targeting human cancers using viral vectors. Novel capsids, synthetic promoters, and therapeutic payloads are being developed and assessed through approaches...

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Detalles Bibliográficos
Autores principales: Swift, Emma A., Pollard, Steven M., Parker, Alan L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Mary Ann Liebert, Inc., publishers 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9700347/
https://www.ncbi.nlm.nih.gov/pubmed/36178346
http://dx.doi.org/10.1089/hum.2022.178
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author Swift, Emma A.
Pollard, Steven M.
Parker, Alan L.
author_facet Swift, Emma A.
Pollard, Steven M.
Parker, Alan L.
author_sort Swift, Emma A.
collection PubMed
description Advances in gene therapy, synthetic biology, cancer genomics, and patient-derived cancer models have expanded the repertoire of strategies for targeting human cancers using viral vectors. Novel capsids, synthetic promoters, and therapeutic payloads are being developed and assessed through approaches such as rational design, pooled library screening, and directed evolution. Ultimately, the goal is to generate precision-engineered viruses that target different facets of tumor cell biology, without compromising normal tissue and organ function. In this study, we briefly review the opportunities for engineering cancer selectivity into viral vectors at both the cell extrinsic and intrinsic level. Such stringently tumor-targeted vectors can subsequently act as platforms for the delivery of potent therapeutic transgenes, including the exciting prospect of immunotherapeutic payloads. These have the potential to eradicate nontransduced cells through stimulation of systemic anticancer immune responses, thereby side-stepping the inherent challenge of achieving gene delivery to the entire cancer cell population. We discuss the importance of using advanced primary human cellular models, such as patient-derived cultures and organoids, to enable rapid screening and triage of novel candidates using disease-relevant models. We believe this combination of improved delivery and selectivity, through novel capsids and promoters, coupled with more potent choices for the combinations of immunotherapy-based payloads seems capable of finally delivering innovative new gene therapies for oncology. Many pieces of the puzzle of how to build a virus capable of targeting human cancers appear to be falling into place.
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spelling pubmed-97003472022-11-30 Engineering Cancer Selective Virotherapies: Are the Pieces of the Puzzle Falling into Place? Swift, Emma A. Pollard, Steven M. Parker, Alan L. Hum Gene Ther Reviews Advances in gene therapy, synthetic biology, cancer genomics, and patient-derived cancer models have expanded the repertoire of strategies for targeting human cancers using viral vectors. Novel capsids, synthetic promoters, and therapeutic payloads are being developed and assessed through approaches such as rational design, pooled library screening, and directed evolution. Ultimately, the goal is to generate precision-engineered viruses that target different facets of tumor cell biology, without compromising normal tissue and organ function. In this study, we briefly review the opportunities for engineering cancer selectivity into viral vectors at both the cell extrinsic and intrinsic level. Such stringently tumor-targeted vectors can subsequently act as platforms for the delivery of potent therapeutic transgenes, including the exciting prospect of immunotherapeutic payloads. These have the potential to eradicate nontransduced cells through stimulation of systemic anticancer immune responses, thereby side-stepping the inherent challenge of achieving gene delivery to the entire cancer cell population. We discuss the importance of using advanced primary human cellular models, such as patient-derived cultures and organoids, to enable rapid screening and triage of novel candidates using disease-relevant models. We believe this combination of improved delivery and selectivity, through novel capsids and promoters, coupled with more potent choices for the combinations of immunotherapy-based payloads seems capable of finally delivering innovative new gene therapies for oncology. Many pieces of the puzzle of how to build a virus capable of targeting human cancers appear to be falling into place. Mary Ann Liebert, Inc., publishers 2022-11-01 2022-11-14 /pmc/articles/PMC9700347/ /pubmed/36178346 http://dx.doi.org/10.1089/hum.2022.178 Text en © Emma A. Swift et al. 2022; Published by Mary Ann Liebert, Inc. https://creativecommons.org/licenses/by/4.0/This Open Access article is distributed under the terms of the Creative Commons License [CC-BY] (http://creativecommons.org/licenses/by/4.0 (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Reviews
Swift, Emma A.
Pollard, Steven M.
Parker, Alan L.
Engineering Cancer Selective Virotherapies: Are the Pieces of the Puzzle Falling into Place?
title Engineering Cancer Selective Virotherapies: Are the Pieces of the Puzzle Falling into Place?
title_full Engineering Cancer Selective Virotherapies: Are the Pieces of the Puzzle Falling into Place?
title_fullStr Engineering Cancer Selective Virotherapies: Are the Pieces of the Puzzle Falling into Place?
title_full_unstemmed Engineering Cancer Selective Virotherapies: Are the Pieces of the Puzzle Falling into Place?
title_short Engineering Cancer Selective Virotherapies: Are the Pieces of the Puzzle Falling into Place?
title_sort engineering cancer selective virotherapies: are the pieces of the puzzle falling into place?
topic Reviews
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9700347/
https://www.ncbi.nlm.nih.gov/pubmed/36178346
http://dx.doi.org/10.1089/hum.2022.178
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