title: Extended release of adenovirus from silica implants in vitro and in vivo.
abstract: Despite promising preclinical results, the clinical benefits of cancer gene therapy have been modest heretofore. The main obstacle continues to be the level and persistence of gene delivery to sufficiently large areas of the tumor. One approach for overcoming this might entail extended local virus release. We studied the utility of silica gel monoliths for delivery of adenovirus to advanced orthotopic gastric and pancreatic cancer tumors. Initially, the biochemical properties of the silica-virus matrix were studied and nearly linear release as a function of time was detected. Virus stayed infective for weeks at +37 degrees C and months at +4 degrees C, which may facilitate storage and distribution. In vivo, extended release of functional replication deficient and also replication-competent, capsid-modified oncolytic viruses was seen. Treatment of mice with pancreatic cancer doubled their survival (P<0.001). Also, silica gel-based delivery slowed the development of antiadenovirus antibodies.
authors.affiliation: Cancer Gene Therapy Group, Molecular Cancer Biology Program and Transplantation Laboratory, University of Helsinki, Helsinki, Finland.
authors.forename: L
authors.initials: L
authors.lastname: Kangasniemi
authors.forename: M
authors.initials: M
authors.lastname: Koskinen
authors.forename: M
authors.initials: M
authors.lastname: Jokinen
authors.forename: M
authors.initials: M
authors.lastname: Toriseva
authors.forename: R
authors.initials: R
authors.lastname: Ala-Aho
authors.forename: V-M
authors.initials: VM
authors.lastname: Kähäri
authors.forename: H
authors.initials: H
authors.lastname: Jalonen
authors.forename: S
authors.initials: S
authors.lastname: Ylä-Herttuala
authors.forename: H
authors.initials: H
authors.lastname: Moilanen
authors.forename: U-H
authors.initials: UH
authors.lastname: Stenman
authors.forename: I
authors.initials: I
authors.lastname: Diaconu
authors.forename: A
authors.initials: A
authors.lastname: Kanerva
authors.forename: S
authors.initials: S
authors.lastname: Pesonen
authors.forename: T
authors.initials: T
authors.lastname: Hakkarainen
authors.forename: A
authors.initials: A
authors.lastname: Hemminki