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Lorena Lerner
Oncorus, Inc.
Corresponding Author
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Oncolytic viruses (OVs) are an emerging therapeutic approach for the treatment of cancer. Clinical benefit has been demonstrated for intratumoral administration, but the therapeutic effectiveness of intravenous delivery has been limited by neutralizing antibody responses against the virus. To circumvent this limitation, we developed Synthetic RNA viruses, a novel approach for intravenous and repeated administration of OVs, consisting of a viral RNA genome (vRNA) formulated within lipid nanoparticles. For two Synthetic RNA virus drug candidates, Seneca Valley virus (SVV) and Coxsackievirus A21 (CVA21), we demonstrate vRNA delivery, viral replication, spread, and lysis of tumor cells leading to potent anti-tumor efficacy, even in the presence of OV neutralizing antibodies in the bloodstream. Synthetic-SVV replication in tumors promoted immune cell infiltration and enhanced anti-tumor activity in combination with anti-PD-1 checkpoint inhibitor. Altogether, the Synthetic RNA virus platform provides an innovative approach that enables repeat intravenous administration of viral immunotherapy.
Keywords
oncolytic virus, immunotherapy, nanoparticle, RNA therapeutics, intravenous, cancer, synthetic RNA virus
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Yes there is potential Competing Interest. This study was sponsored by Oncorus, Inc. E.M. Kennedy, A. Denslow, J. Hewett, L. Kong, A. De Almeida, J. Bryant, J.S. Lee, J. Jacques, S. Feau, M. Hayes, E.L. McMichael, A. Rhameh (at the time the study was conducted), L. Herschelman (at the time the study was conducted), D. Douglas (at the time the study was conducted), J. Spinale, S. Adhikari, J. Deterling, M. Scott, B.B. Haines, T. Ashburn, C. Quéva, L. Lerner are all employees of Oncorus, Inc. No other authors have any conflicts of interest to disclose.
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- EditorialChecklist.pdf
Editorial Policy Checklist
- ReportingSummary.pdf
Reporting Summary
- SupplementalFigures.pdf
Supplemental Figures
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This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Article
Lorena Lerner
Oncorus, Inc.
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 27 May, 2021
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Oncolytic viruses (OVs) are an emerging therapeutic approach for the treatment of cancer. Clinical benefit has been demonstrated for intratumoral administration, but the therapeutic effectiveness of intravenous delivery has been limited by neutralizing antibody responses against the virus. To circumvent this limitation, we developed Synthetic RNA viruses, a novel approach for intravenous and repeated administration of OVs, consisting of a viral RNA genome (vRNA) formulated within lipid nanoparticles. For two Synthetic RNA virus drug candidates, Seneca Valley virus (SVV) and Coxsackievirus A21 (CVA21), we demonstrate vRNA delivery, viral replication, spread, and lysis of tumor cells leading to potent anti-tumor efficacy, even in the presence of OV neutralizing antibodies in the bloodstream. Synthetic-SVV replication in tumors promoted immune cell infiltration and enhanced anti-tumor activity in combination with anti-PD-1 checkpoint inhibitor. Altogether, the Synthetic RNA virus platform provides an innovative approach that enables repeat intravenous administration of viral immunotherapy.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Yes there is potential Competing Interest. This study was sponsored by Oncorus, Inc. E.M. Kennedy, A. Denslow, J. Hewett, L. Kong, A. De Almeida, J. Bryant, J.S. Lee, J. Jacques, S. Feau, M. Hayes, E.L. McMichael, A. Rhameh (at the time the study was conducted), L. Herschelman (at the time the study was conducted), D. Douglas (at the time the study was conducted), J. Spinale, S. Adhikari, J. Deterling, M. Scott, B.B. Haines, T. Ashburn, C. Quéva, L. Lerner are all employees of Oncorus, Inc. No other authors have any conflicts of interest to disclose.
This is a list of supplementary files associated with this preprint. Click to download.
- EditorialChecklist.pdf
Editorial Policy Checklist
- ReportingSummary.pdf
Reporting Summary
- SupplementalFigures.pdf
Supplemental Figures
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