title: Oncolytic polio virotherapy of cancer.
abstract: Recently, the century-old idea of targeting cancer with viruses (oncolytic viruses) has come of age, and promise has been documented in early stage and several late-stage clinical trials in a variety of cancers. Although originally prized for their direct tumor cytotoxicity (oncolytic virotherapy), recently, the proinflammatory and immunogenic effects of viral tumor infection (oncolytic immunotherapy) have come into focus. Indeed, a capacity for eliciting broad, sustained antineoplastic effects stemming from combined direct viral cytotoxicity, innate antiviral activation, stromal proinflammatory stimulation, and recruitment of adaptive immune effector responses is the greatest asset of oncolytic viruses. However, it also is the source for enormous mechanistic complexity that must be considered for successful clinical translation. Because of fundamentally different relationships with their hosts (malignant or not), diverse replication strategies, and distinct modes of tumor cytotoxicity/killing, oncolytic viruses should not be referred to collectively. These agents must be evaluated based on their individual merits. In this review, the authors highlight key mechanistic principles of cancer treatment with the polio:rhinovirus chimera PVSRIPO and their implications for oncolytic immunotherapy in the clinic.
authors.affiliation: Department of Surgery, Duke Cancer Institute, Duke University Medical Center, Durham, North Carolina; Division of Neurosurgery Duke Cancer Institute, Duke University Medical Center, Durham, North Carolina; Department of Molecular Genetics and Microbiology, Duke Cancer Institute, Duke University Medical Center, Durham, North Carolina.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Brown
authors.forename: Elena Y
authors.initials: EY
authors.lastname: Dobrikova
authors.forename: Mikhail I
authors.initials: MI
authors.lastname: Dobrikov
authors.forename: Ross W
authors.initials: RW
authors.lastname: Walton
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Gemberling
authors.forename: Smita K
authors.initials: SK
authors.lastname: Nair
authors.forename: Annick
authors.initials: A
authors.lastname: Desjardins
authors.forename: John H
authors.initials: JH
authors.lastname: Sampson
authors.forename: Henry S
authors.initials: HS
authors.lastname: Friedman
authors.forename: Allan H
authors.initials: AH
authors.lastname: Friedman
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Tyler
authors.forename: Darell D
authors.initials: DD
authors.lastname: Bigner
authors.forename: Matthias
authors.initials: M
authors.lastname: Gromeier
mesh_terms: D006801:Humans; D007113:Immunity, Innate / Q000235:genetics*; D007167:Immunotherapy; D009369:Neoplasms / Q000235:genetics* / Q000628:therapy* / Q000821:virology; D050130:Oncolytic Virotherapy; D050504:Oncolytic Viruses / Q000235:genetics*; D011051:Poliomyelitis / Q000235:genetics; D011991:Receptors, Virus / Q000276:immunology; D053586:Virus Internalization
chemical_list: D011991:Receptors, Virus; C066100:poliovirus receptor
keywords: CD155; eIF4G; innate antiviral response; interferon; internal ribosomal entry site; nectin-like molecule 5; oncolytic virus; poliovirus; translation