title: A Multi Targeting Conditionally Replicating Adenovirus Displays Enhanced Oncolysis while Maintaining Expression of Immunotherapeutic Agents.
abstract: Studies have demonstrated that oncolytic adenoviruses based on a 24 base pair deletion in the viral E1A gene (D24) may be promising therapeutics for treating a number of cancer types. In order to increase the therapeutic potential of these oncolytic viruses, a novel conditionally replicating adenovirus targeting multiple receptors upregulated on tumors was generated by incorporating an Ad5/3 fiber with a carboxyl terminus RGD ligand. The virus displayed full cytopathic effect in all tumor lines assayed at low titers with improved cytotoxicity over Ad5-RGD D24, Ad5/3 D24 and an HSV oncolytic virus. The virus was then engineered to deliver immunotherapeutic agents such as GM-CSF while maintaining enhanced heterogenic oncolysis.
authors.affiliation: Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.|Department of Neurosurgery, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
authors.forename: G Clement
authors.initials: GC
authors.lastname: Dobbins
authors.affiliation: Cancer Biology Division, Department of Radiation Oncology, School of Medicine, Washington University in St. Louis, St. Louis, Missouri, United States of America.
authors.forename: Hideyo
authors.initials: H
authors.lastname: Ugai
authors.affiliation: Biologic Therapeutics Center, Department of Radiation Oncology, School of Medicine, Washington University in St. Louis, Missouri, United States of America.
authors.forename: David T
authors.initials: DT
authors.lastname: Curiel
authors.affiliation: Department of Neurosurgery, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
authors.forename: G Yancey
authors.initials: GY
authors.lastname: Gillespie
mesh_terms: D000256:Adenoviridae; D017500:Adenovirus E1A Proteins / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D045744:Cell Line, Tumor; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D009369:Neoplasms / Q000628:therapy*; D009842:Oligopeptides / Q000235:genetics / Q000378:metabolism; D050130:Oncolytic Virotherapy / Q000379:methods*; D050504:Oncolytic Viruses / Q000235:genetics / Q000378:metabolism; D017384:Sequence Deletion; D014779:Virus Replication
chemical_list: D017500:Adenovirus E1A Proteins; D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid