title: Potential for Improving Potency and Specificity of Reovirus Oncolysis with Next-Generation Reovirus Variants.
abstract: Viruses that specifically replicate in tumor over normal cells offer promising cancer therapies. Oncolytic viruses (OV) not only kill the tumor cells directly; they also promote anti-tumor immunotherapeutic responses. Other major advantages of OVs are that they dose-escalate in tumors and can be genetically engineered to enhance potency and specificity. Unmodified wild type reovirus is a propitious OV currently in phase I-III clinical trials. This review summarizes modifications to reovirus that may improve potency and/or specificity during oncolysis. Classical genetics approaches have revealed reovirus variants with improved adaptation towards tumors or with enhanced ability to establish specific steps of virus replication and cell killing among transformed cells. The recent emergence of a reverse genetics system for reovirus has provided novel strategies to fine-tune reovirus proteins or introduce exogenous genes that could promote oncolytic activity. Over the next decade, these findings are likely to generate better-optimized second-generation reovirus vectors and improve the efficacy of oncolytic reotherapy.
authors.affiliation: Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, AB T6G 2E1, Canada. adilm@ualberta.ca.
authors.forename: Adil
authors.initials: A
authors.lastname: Mohamed
authors.affiliation: Department of Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada. rnjohnst@ucalgary.ca.
authors.forename: Randal N
authors.initials: RN
authors.lastname: Johnston
authors.affiliation: Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, AB T6G 2E1, Canada. shmulevi@ualberta.ca.
authors.forename: Maya
authors.initials: M
authors.lastname: Shmulevitz
mesh_terms: D002986:Clinical Trials as Topic; D055808:Drug Discovery / Q000379:methods*; D050130:Oncolytic Virotherapy / Q000379:methods*; D050504:Oncolytic Viruses / Q000302:isolation & purification* / Q000502:physiology*; D012087:Reoviridae / Q000302:isolation & purification* / Q000502:physiology*
keywords: attachment; cancer; oncolytic virus; reovirus; replication; reverse genetics; uncoating