Development of intravenously administered synthetic RNA virus immunotherapy for the treatment of cancer

Edward M. Kennedy (), Agnieszka Denslow, Jacqueline Hewett, Lingxin Kong, Ana Almeida, Jeffrey D. Bryant, Jennifer S. Lee, Judy Jacques, Sonia Feau, Melissa Hayes, Elizabeth L. McMichael, Daniel Wambua, Terry Farkaly, Amal A Rahmeh, Lauren Herschelman, Danielle Douglas, Jacob Spinale, Sanmit Adhikari, Jessica Deterling, Matt Scott, Brian B. Haines, Mitchell H. Finer, Ted T Ashburn, Christophe Quéva and Lorena Lerner
Additional contact information
Edward M. Kennedy: Oncorus, Inc.
Agnieszka Denslow: Oncorus, Inc.
Jacqueline Hewett: Oncorus, Inc.
Lingxin Kong: Oncorus, Inc.
Ana Almeida: Oncorus, Inc.
Jeffrey D. Bryant: Oncorus, Inc.
Jennifer S. Lee: Oncorus, Inc.
Judy Jacques: Oncorus, Inc.
Sonia Feau: Oncorus, Inc.
Melissa Hayes: Oncorus, Inc.
Elizabeth L. McMichael: Oncorus, Inc.
Daniel Wambua: Oncorus, Inc.
Terry Farkaly: Oncorus, Inc.
Amal A Rahmeh: Oncorus, Inc.
Lauren Herschelman: Oncorus, Inc.
Danielle Douglas: Oncorus, Inc.
Jacob Spinale: Oncorus, Inc.
Sanmit Adhikari: Oncorus, Inc.
Jessica Deterling: Oncorus, Inc.
Matt Scott: Oncorus, Inc.
Brian B. Haines: Oncorus, Inc.
Mitchell H. Finer: Oncorus, Inc.
Ted T Ashburn: Oncorus, Inc.
Christophe Quéva: Oncorus, Inc.
Lorena Lerner: Oncorus, Inc.

Nature Communications, 2022, vol. 13, issue 1, 1-13

Abstract: Abstract The therapeutic effectiveness of oncolytic viruses (OVs) delivered intravenously is limited by the development of neutralizing antibody responses against the virus. To circumvent this limitation and to enable repeated systemic administration of OVs, here we develop Synthetic RNA viruses 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, we demonstrate vRNA delivery and replication, virus assembly, 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 promotes immune cell infiltration, remodeling of the tumor microenvironment, and enhances the activity of anti-PD-1 checkpoint inhibitor. In mouse and non-human primates, Synthetic-SVV is well tolerated reaching exposure well above the requirement for anti-tumor activity. Altogether, the Synthetic RNA virus platform provides an approach that enables repeat intravenous administration of viral immunotherapy.

Date: 2022
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DOI: 10.1038/s41467-022-33599-w

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