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Handling of the Cotton Rat in Studies for the Pre-clinical Evaluation of Oncolytic Viruses
Published on: November 24, 2014
The reovirus variant RP116 is oncolytic in immunocompetent models and generates reduced neutralizing antibodies to
Ki-Hoon Song1, Xiao Xiang2,3, So Hyun Lee1
1ViroCure, #502, Ace TwinTower 1, 285 Digital-ro, Guro-gu, Seoul 08381, Republic of Korea.
Abstract:
The mammalian reovirus Type 3 Dearing (T3D) is a naturally occurring oncolytic virus. We previously identified a T3D variant isolated from persistently infected cancer cells that has a premature stop codon mutation in the S1 gene, generating a truncated σ1-attachment protein that lacks the globular head. We now report on the molecular characterization of this variant, named RP116, and assess its antitumor potential in human cancer cells and syngeneic mouse models. RP116 replicates efficiently in several cancer cell lines, shows reduced dependency for the JAM-A receptor, significantly decreases tumor growth in syngeneic models when injected either intratumorally or intravenously, and generates long-term cures and immune memory in combination with checkpoint inhibitors. Finally, we demonstrate that RP116 infection in mice leads to reduced production of neutralizing antibodies directed against reovirus T3D, preserving the efficacy of subsequent reovirus treatment. These results establish the value of developing RP116 as an additional oncolytic reovirus platform.
Insights
A novel reovirus variant, RP116, effectively targets cancer cells and reduces tumor growth in mice. This oncolytic virus also generates immune memory and avoids antibody neutralization, enhancing future treatments.
Area of Science:
- Virology
- Immunology
- Oncology
Background:
- Mammalian reovirus Type 3 Dearing (T3D) is a naturally occurring oncolytic virus.
- A T3D variant (RP116) with a truncated σ1-attachment protein was previously identified.
Purpose of the Study:
- To characterize RP116 and evaluate its antitumor potential.
- To assess RP116's efficacy in human cancer cells and mouse models.
- To investigate RP116's impact on anti-reovirus neutralizing antibodies.
Main Methods:
- Molecular characterization of the RP116 variant.
- In vitro replication assays in human cancer cell lines.
- In vivo studies using syngeneic mouse models (intratumoral and intravenous injection).
- Combination therapy with checkpoint inhibitors.
- Assessment of neutralizing antibody production in mice.
Main Results:
- RP116 replicates efficiently in various cancer cell lines.
- RP116 exhibits reduced dependency on the JAM-A receptor.
- Significant tumor growth reduction and long-term cures were observed in mouse models.
- Combination therapy with checkpoint inhibitors generated durable immune memory.
- RP116 infection reduced neutralizing antibody production against T3D, preserving subsequent treatment efficacy.
Conclusions:
- RP116 demonstrates significant antitumor potential as an oncolytic virus.
- RP116's reduced receptor dependency and immune-sparing properties are advantageous.
- RP116 represents a promising platform for developing novel oncolytic reovirus therapies.
