Engineered Oncolytic Poliovirus PVSRIPO Subverts MDA5-Dependent Innate Immune Responses in Cancer Cells

Journal of Virology
Ross W WaltonMatthias Gromeier

Abstract

We are pursuing cancer immunotherapy with a neuro-attenuated recombinant poliovirus, PVSRIPO. PVSRIPO is the live attenuated type 1 (Sabin) poliovirus vaccine carrying a heterologous internal ribosomal entry site (IRES) of human rhinovirus type 2 (HRV2). Intratumoral infusion of PVSRIPO is showing promise in the therapy of recurrent WHO grade IV malignant glioma (glioblastoma), a notoriously treatment-refractory cancer with dismal prognosis. PVSRIPO exhibits profound cytotoxicity in infected neoplastic cells expressing the poliovirus receptor CD155. In addition, it elicits intriguing persistent translation and replication, giving rise to sustained type I interferon (IFN)-dominant proinflammatory stimulation of antigen-presenting cells. A key determinant of the inflammatory footprint generated by neoplastic cell infection and its role in shaping the adaptive response after PVSRIPO tumor infection is the virus's inherent relationship to the host's innate antiviral response. In this report, we define subversion of innate host immunity by PVSRIPO, enabling productive viral translation and cytopathogenicity with extremely low multiplicities of infection in the presence of an active innate antiviral IFN response.IMPORTANCE Engaging i...Continue Reading

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Citations

Feb 16, 2019·Cancers·Miika Martikainen, Magnus Essand
May 19, 2019·Cancers·Cormac McCarthyMihnea Bostina
Aug 11, 2020·Current Opinion in Virology·Mubeen M MosahebMatthias Gromeier
Mar 28, 2021·Annals of Oncology : Official Journal of the European Society for Medical Oncology·A B CarpenterS Hanft
Apr 21, 2021·Journal for Immunotherapy of Cancer·Georgia M BeasleyApril Ks Salama
Aug 5, 2021·Signal Transduction and Targeted Therapy·Danyang Li, Minghua Wu

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