A conditionally replicative adenovirus with enhanced infectivity shows improved oncolytic potency.
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.
Suzuki
K
K
Gene Therapy Center, University of Alabama at Birmingham, 35294-3300, USA.
Fueyo
J
J
Krasnykh
V
V
Reynolds
P N
PN
Curiel
D T
DT
Alemany
R
R
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
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