Improved oncolytic activity of a reovirus mutant that displays enhanced virus spread due to reduced cell attachment

Cristi, Francisca; Walters, Maiah; Narayan, Nashae; Agopsowicz, Kate; Hitt, Mary M.; Shmulevitz, Maya

doi:10.1016/j.omto.2023.100743

Cited by 2 publications

References 77 publications

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Mathematical Modelling of Reoviruses in Cancer Cell Cultures

Baabdulla,

Cristi,

Shmulevitz

et al. 2024

Preprint

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Oncolytic virotherapy has emerged as a potential cancer therapy, utilizing viruses to selectively target and replicate within cancer cells while preserving normal cells. In this paper, we investigate the oncolytic potential of unmodified reovirus T3wt relative to a mutated variant SV5. In animal cancer cell monolayer experiments it was found that SV5 was more oncolytic relative to T3wt. SV5 forms larger sized plaques on cancer cell monolayers and spreads to farther distances from the initial site of infection as compared to T3wt. Paradoxically, SV5 attaches to cancer cells less efficiently than T3wt, which lead us to hypothesize that there might be an optimal binding affinity with maximal oncolytic activity. To understand the relationship between the binding process and virus spread for T3wt and SV5, we employ mathematical modelling. A reaction-diffusion model is applied, which is fit to the available data and then validated on data that were not used for the fit. Analysis of our model shows that there is an optimal binding rate that leads to maximum viral infection of the cancer monolayer, and we estimate this value for T3wt and SV5. Moreover, we find that the viral burst size is an important parameter for viral spread, and that a combination of efficient binding and large burst sizes is a promising direction to further develop anti-cancer viruses.

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Mathematical Modelling of Reoviruses in Cancer Cell Cultures

Baabdulla,

Cristi,

Shmulevitz

et al. 2024

Preprint

Self Cite

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Neutrophils in oncolytic virus immunotherapy

Zhou,

Zhang,

Sun

et al. 2024

Front. Immunol.

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Oncolytic viruses have emerged as a highly promising modality for cancer treatment due to their ability to replicate specifically within tumors, carry therapeutic genes, and modulate the immunosuppressive tumor microenvironment through various mechanisms. Additionally, they show potential synergy with immune checkpoint inhibitors. A study report indicates that from 2000 to 2020, 49.5% of oncolytic viruses were administered intratumorally and 35% intravenously during clinical trials. However, both administration methods face significant challenges, particularly with intravenous delivery, which encounters issues such as non-specific tissue uptake, neutralizing antibody responses, and antiviral effects mediated by various immune cells. Despite extensive research into the antiviral roles of CD8+ T cells and NK cells in oncolytic virus therapy, neutrophils—constituting approximately 50% to 70% of human peripheral blood leukocytes—have received relatively little attention. Neutrophils are the most abundant leukocyte subset in peripheral circulation, known for their phagocytic activity. Beyond their traditional roles in bacterial and fungal infections, emerging literature suggests that neutrophils also play a critical role in the body’s antiviral responses. Given the gaps in understanding the role of neutrophils in oncolytic virus therapy, this article reviews current literature on this topic. It aims to provide a theoretical foundation for developing oncolytic virus-based cancer therapies and enhancing their anti-tumor efficacy in future clinical treatments.

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Improved oncolytic activity of a reovirus mutant that displays enhanced virus spread due to reduced cell attachment

Cited by 2 publications

References 77 publications

Mathematical Modelling of Reoviruses in Cancer Cell Cultures

Mathematical Modelling of Reoviruses in Cancer Cell Cultures

Neutrophils in oncolytic virus immunotherapy

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