Efficacy of oncolytic reovirus against human gastric cancer with peritoneal metastasis in experimental animal model

Kawaguchi,

doi:10.3892/ijo_00000795

Cited by 20 publications

(16 citation statements)

References 26 publications

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“…However, H1437 cells were generated from a lung metastasis. Moreover, data from mouse models and clinical trials indicate that T3D (Reolysin) can target and kill metastases in mouse models and humans [22,38,39]. Thus, whether cell lines derive from primary versus metastatic tumors is unlikely to underlie strain-specific differences in cell killing.…”

Section: Discussionmentioning

confidence: 99%

Serotype-Specific Killing of Large Cell Carcinoma Cells by Reovirus

Simon

Howells

Stuart

2017

Viruses

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Reovirus is under development as a therapeutic for numerous types of cancer. In contrast to other oncolytic viruses, the safety and efficacy of reovirus have not been improved through genetic manipulation. Here, we tested the oncolytic capacity of recombinant strains (rs) of prototype reovirus laboratory strains T1L and T3D (rsT1L and rsT3D, respectively) in a panel of non-small cell lung cancer (NSCLC) cell lines. We found that rsT1L was markedly more cytolytic than rsT3D in the large cell carcinoma cell lines tested, whereas killing of adenocarcinoma cell lines was comparable between rsT1L and rsT3D. Importantly, non-recombinant T1L and T3D phenocopied the kinetics and magnitude of cell death induced by recombinant strains. We identified gene segments L2, L3, and M1 as viral determinants of strain-specific differences cell killing of the large cell carcinoma cell lines. Together, these results indicate that recombinant reoviruses recapitulate the cell killing properties of non-recombinant, tissue culture-passaged strains. These studies provide a baseline for the use of reverse genetics with the specific objective of engineering more effective reovirus oncolytics. This work raises the possibility that type 1 reoviruses may have the capacity to serve as more effective oncolytics than type 3 reoviruses in some tumor types.

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Section: Discussionmentioning

confidence: 99%

Serotype-Specific Killing of Large Cell Carcinoma Cells by Reovirus

Simon

Howells

Stuart

2017

Viruses

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“…In 2010, a study evaluating reovirus in Ras-activated gastric cancer models showed encouraging efficacy. 30 …”

Section: Upper Gastrointestinal Tract Malignanciesmentioning

confidence: 99%

Oncolytic virotherapy in upper gastrointestinal tract cancers

Yokoda

Nagalo

Arora

et al. 2018

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Upper gastrointestinal tract malignancies are among the most challenging cancers with regard to response to treatment and prognosis. Cancers of the esophagus, stomach, pancreas, liver, and biliary tree have dismal 5-year survival, and very modest improvements in this rate have been made in recent times. Oncolytic viruses are being developed to address these malignancies, with a focus on high safety profiles and low off-target toxicities. Each viral platform has evolved to enhance oncolytic potency and the clinical response to either single-agent viral therapy or combined viral treatment with radiotherapy and chemotherapy. A panel of genomic alterations, chimeric proteins, and pseudotyped capsids are the breakthroughs for vector success. This article revisits developments for each viral platform to each tumor type, in an attempt to achieve maximum tumor selectivity. From the bench to clinical trials, the scope of this review is to highlight the beginnings of translational oncolytic virotherapy research in upper gastrointestinal tract malignancies and provide a bioengineering perspective of the most promising platforms.

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“…Early preclinical studies with Reovirus demonstrated its ability to infect, replicate and induce cancer cell specific apoptosis with no activity in normal tissue across several gastrointestinal malignancies [18,19,20]. Reolysin (pelareorep) is a propriety formulation of the naturally occurring Reovirus Serotype3-Dearing strain, a live replication-competent Reovirus that has demonstrated cytotoxic effects on cancer cells that harbored mutations in the RAS signaling pathway with a tolerable safety profile [17,21,22,23,24].…”

Section: Reovirusmentioning

confidence: 99%

The Continued Promise and Many Disappointments of Oncolytic Virotherapy in Gastrointestinal Malignancies

Ahn

Bekaii‐Saab

2017

Biomedicines

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Oncolytic virotherapy represents a novel therapeutic strategy in the treatment of gastrointestinal malignancies. Oncolytic viruses, including genetically engineered and naturally occurring viruses, can selectively replicate in and induce tumor cell apoptosis without harming normal tissues, thus offering a promising tool in the armamentarium for cancer therapy. While this approach has garnered much interest over the past several decades, there has not been significant headway across various tumor types. The recent approval of talimogene laherparepvec, a second-generation oncolytic herpes simplex virus type-1, for the treatment of metastatic melanoma, confirms the therapeutic potential of oncolytic viral therapy. Herein, we will highlight and review the role of oncolytic viral therapy in gastrointestinal malignancies while discussing its limitations and potential alternative mechanisms to improve its treatment efficacy.

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Efficacy of oncolytic reovirus against human gastric cancer with peritoneal metastasis in experimental animal model

Cited by 20 publications

References 26 publications

Serotype-Specific Killing of Large Cell Carcinoma Cells by Reovirus

Serotype-Specific Killing of Large Cell Carcinoma Cells by Reovirus

Oncolytic virotherapy in upper gastrointestinal tract cancers

The Continued Promise and Many Disappointments of Oncolytic Virotherapy in Gastrointestinal Malignancies

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