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Engineering cancer selective virotherapies: are the pieces of the puzzle falling into place?

Swift, Emma A., Pollard, Steven M. and Parker, Alan L. ORCID: 2022. Engineering cancer selective virotherapies: are the pieces of the puzzle falling into place? Human Gene Therapy 33 (21-22) 10.1089/hum.2022.178

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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 via 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 tumour cell biology, without compromising normal tissue and organ function. Here, we briefly review the opportunities for engineering cancer selectivity into viral vectors at both the cell extrinsic and intrinsic level. Such stringently tumour-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 non-transduced cells through stimulation of systemic anti-cancer 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 human cellular 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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Publisher: Mary Ann Liebert
ISSN: 1043-0342
Funders: Cancer Research UK
Date of First Compliant Deposit: 5 October 2022
Date of Acceptance: 30 September 2022
Last Modified: 25 May 2023 11:39

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