title: The oncolytic virus, pelareorep, as a novel anticancer agent: a review.
abstract: Pelareorep (REOLYSIN®) is an investigational new drug, a proprietary formulation consisting of a live, replication-competent, naturally occurring Reovirus Type 3 Dearing strain. Through several preclinical studies it was determined that reovirus can exhibit profound cytotoxic effects on cancer cells predominantly with an activated RAS-signalling pathway. Moreover, it was discovered that reoviruses can "hitchhike" on peripheral blood mononuclear cells and dendritic cells, thereby evading neutralizing antibodies of the host immune system. Cell carriage, targeted delivery, triggering host immune response and other inherent characteristics of the reovirus led to its further advancement into cancer therapy. When injected into Sprague-Dawley rats, the viral routes of clearance, predominantly through the spleen and liver, remained consistent with earlier studies. Toxicology findings were considered incidental and not associated with pelareorep when tested in animal models. Pelareorep demonstrated a high level of homogeneity at the amino acid level and genetic stability when compared to the master and working virus banks. The drug is manufactured in a 100 L bioreactor after which it is purified and formulated for use in pre-clinical, clinical and research studies. Over the past few decades, we have witnessed a paradigm shift from conventional therapy to the conceivable use of oncolytic viruses for the treatment of cancer. This review will detail pre-clinical evidence of anticancer activity of pelareorep that has led to extensive clinical development. Several Phase I-II clinical trials have been completed or are ongoing in cancer patients on a broad spectrum of solid tumors and hematologic malignancies.
authors.affiliation: Oncolytics Biotech Inc., 210, 1167 Kensington Cr. NW, Calgary, AB, T2N 1X7, Canada.
authors.forename: Romit
authors.initials: R
authors.lastname: Chakrabarty
authors.forename: Hue
authors.initials: H
authors.lastname: Tran
authors.forename: Giovanni
authors.initials: G
authors.lastname: Selvaggi
authors.forename: Allison
authors.initials: A
authors.lastname: Hagerman
authors.forename: Brad
authors.initials: B
authors.lastname: Thompson
authors.forename: Matt
authors.initials: M
authors.lastname: Coffey
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism; D002986:Clinical Trials as Topic; D006801:Humans; D007167:Immunotherapy; D050504:Oncolytic Viruses / Q000378:metabolism*; D012087:Reoviridae / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor