title: A conditionally replicative adenovirus with enhanced infectivity shows improved oncolytic potency.
abstract: The absence or the presence of low levels of the Coxsackievirus and adenovirus receptor (CAR) on several tumor types might limit the efficacy of recently proposed tumor-specific or conditionally replicative adenoviruses (CRAds). To address this issue, we used a genetic modification of the fiber knob in the context of an E1A-defective CRAd to allow CAR-independent target cell infection as a means to enhance oncolytic potency. Such infectivity-enhanced CRAd showed higher replication, more efficient infection, and lysis of tumor cells in vitro. Of note, the improved antitumor effect of the fiber-modified CRAd could be demonstrated in vivo. We conclude that the combination of genomic modification to achieve tumor-selective replication and capsid modification to enhance infectivity yields more potent oncolytic adenoviruses for use in cancer treatment.
authors.affiliation: Gene Therapy Center, University of Alabama at Birmingham, 35294-3300, USA.
authors.forename: K
authors.initials: K
authors.lastname: Suzuki
authors.forename: J
authors.initials: J
authors.lastname: Fueyo
authors.forename: V
authors.initials: V
authors.lastname: Krasnykh
authors.forename: P N
authors.initials: PN
authors.lastname: Reynolds
authors.forename: D T
authors.initials: DT
authors.lastname: Curiel
authors.forename: R
authors.initials: R
authors.lastname: Alemany
mesh_terms: D000256:Adenoviridae / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D017500:Adenovirus E1A Proteins; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D005260:Female; D005562:Formazans; D005822:Genetic Vectors; D006801:Humans; D007159:Immunologic Tests; D066298:In Vitro Techniques; D008156:Luciferases / Q000378:metabolism; D008175:Lung Neoplasms / Q000628:therapy* / Q000821:virology; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009842:Oligopeptides / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000628:therapy* / Q000821:virology; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured / Q000821:virology; D014779:Virus Replication; D014780:Viruses
chemical_list: D017500:Adenovirus E1A Proteins; D005562:Formazans; D009842:Oligopeptides; D016160:Retinoblastoma Protein; C059088:1,5-bis(2-methoxy-4-nitro-5-sulfophenyl)-3-((phenylamino)carbonyl)formazan; C047981:arginyl-glycyl-aspartic acid; D008156:Luciferases