Designing and Building Oncolytic Viruses

Maroun, Justin W.; Muñoz-Alía, Miguel Ángel; Ammayappan, Arun; Schulze, Autumn J; Peng, Kah Whye; Russell, Stephen J.

doi:10.2217/fvl-2016-0129

Cited by 124 publications

(98 citation statements)

References 189 publications

(131 reference statements)

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“…Moreover, expressing therapeutic molecules through OAds provides the unique opportunity to attain targeting tumours using therapeutic agents with unacceptable systemic toxicity profiles 14,15 .…”

Section: Introductionmentioning

confidence: 99%

Transgene codon usage drives viral fitness and therapeutic efficacy in oncolytic adenoviruses

Núñez-Manchón

Farrera-Sal

Castellano

et al. 2020

Preprint

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Arming oncolytic adenoviruses with therapeutic transgenes is a well-established strategy for multimodal tumour attack. However, this strategy sometimes leads to unexpected attenuated viral replication and a loss of oncolytic effects, preventing these viruses from reaching the clinic. Previous work has shown that altering codon usage in viral genes can hamper viral fitness. Here, we have analysed how transgene codon usage impacts viral replication and oncolytic activity. We observe that, although transgenes with optimised codons show high expression levels at a first round of infection, they impair viral fitness and are therefore not expressed in a sustained manner. Conversely, transgenes encoded by suboptimal codons do not compromise viral replication and are thus stably expressed over time allowing a greater oncolytic activity both in vitro and in vivo. Altogether, our work shows that fine-tuning codon usage leads to a concerted optimisation of transgene expression and viral replication paving the way for the rational design of more efficacious oncolytic therapies.

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Section: Introductionmentioning

confidence: 99%

Transgene codon usage drives viral fitness and therapeutic efficacy in oncolytic adenoviruses

Núñez-Manchón

Farrera-Sal

Castellano

et al. 2020

Preprint

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“…OVs are modified or selected to preferentially infect tumor cells. (4) Several OVs preferentially bind to entry receptors disproportionately exhibited on tumor cells, increasing specificity for tumor cell infectivity. (5) Viral entry receptors can also be engineered to target tumor cells.…”

Section: Mechanism Of Actionmentioning

confidence: 99%

“…Initial inoculum size and time to peak viral levels may vary. (4) The inoculum may face significant barriers to intratumoral dissemination such as heterogeneous tumor perfusion and high interstitial pressures. (3, 79)…”

Section: Current Challengesmentioning

confidence: 99%

The Role of Oncolytic Viruses in the Treatment of Melanoma

et al. 2018

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Talimogene laherparepvec (T-VEC) is the first OV approved for the treatment of melanoma and presents new challenges as it enters the clinical setting. Several other OVs are at various stages of clinical and pre-clinical development for the treatment of melanoma. Reports from phase Ib-III clinical trials combining T-VEC with checkpoint blockade are encouraging and demonstrate potential added benefit of combination immunotherapy. OVs have recently emerged as a standard treatment option for patients with advanced melanoma. Several OVs and therapeutic combinations are in development. Immunooncolytic virotherapy combined with immune checkpoint inhibitors is promising for the treatment of advanced melanoma.

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“…Many genetically modified OVs have been evaluated in clinical trials, as shown in Table 2; such OVs include AdV, VACV, and HSV. OVs mainly genetically modified through the deletion of virulence genes to improve the safety and insertion of foreign genes and improve antitumor efficacy or tumor targeting ability of OVs [77]. The genetic modifications of OVs can be…”

Section: Genetic Modifications Of Ovsmentioning

confidence: 99%

Development of oncolytic virotherapy: from genetic modification to combination therapy

et al. 2020

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Oncolytic virotherapy (OVT) is a novel form of immunotherapy using natural or genetically modified viruses to selectively replicate in and kill malignant cells. Many genetically modified oncolytic viruses (OVs) with enhanced tumor targeting, antitumor efficacy, and safety have been generated, and some of which have been assessed in clinical trials. Combining OVT with other immunotherapies can remarkably enhance the antitumor efficacy. In this work, we review the use of wild-type viruses in OVT and the strategies for OV genetic modification. We also review and discuss the combinations of OVT with other immunotherapies.

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Designing and Building Oncolytic Viruses

Cited by 124 publications

References 189 publications

Transgene codon usage drives viral fitness and therapeutic efficacy in oncolytic adenoviruses

Transgene codon usage drives viral fitness and therapeutic efficacy in oncolytic adenoviruses

The Role of Oncolytic Viruses in the Treatment of Melanoma

Development of oncolytic virotherapy: from genetic modification to combination therapy

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