title: Evaluation of a selectively oncolytic adenovirus for local and systemic treatment of cervical cancer.
abstract: Treatment options for disseminated cervical cancer remain inadequate. Here, we investigated a strategy featuring Ad5-Delta 24 RGD, an oncolytic adenovirus replication-competent selectively in cells defective in the Rb-p16 pathway, such as most cervical cancer cells. The viral fiber contains an alpha(v)beta(3) and alpha(v)beta(5) integrin-binding RGD-4C motif, allowing coxsackie-adenovirus receptor-independent infection. These integrins have been reported to be frequently upregulated in cervical cancer. Oncolysis of cervical cancer cells was similar to a wild-type control in vitro. In an animal model of cervical cancer, the therapeutic efficacy of Ad5-Delta 24 RGD could be demonstrated for both intratumoral and intravenous application routes. Biodistribution was determined following intravenous administration to mice. Further preclinical safety data were obtained by demonstrating lack of replication of the agent in human peripheral blood mononuclear cells. These results suggest that Ad5-Delta 24 RGD could be useful for local or systemic treatment of cervical cancer in patients with disease resistant to currently available modalities.
authors.affiliation: Division of Human Gene Therapy, Department of Medicine, Gene Therapy Center, University of Alabama at Birmingham, USA.
authors.forename: Gerd J
authors.initials: GJ
authors.lastname: Bauerschmitz
authors.forename: Anna
authors.initials: A
authors.lastname: Kanerva
authors.forename: Minghui
authors.initials: M
authors.lastname: Wang
authors.forename: Isabell
authors.initials: I
authors.lastname: Herrmann
authors.forename: Denise R
authors.initials: DR
authors.lastname: Shaw
authors.forename: Theresa V
authors.initials: TV
authors.lastname: Strong
authors.forename: Renee
authors.initials: R
authors.lastname: Desmond
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Rein
authors.forename: Peter
authors.initials: P
authors.lastname: Dall
authors.forename: David T
authors.initials: DT
authors.lastname: Curiel
authors.forename: Akseli
authors.initials: A
authors.lastname: Hemminki
mesh_terms: D000256:Adenoviridae; D000818:Animals; D001691:Biological Therapy / Q000379:methods; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007963:Leukocytes, Mononuclear; D051379:Mice; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000628:therapy*; D014779:Virus Replication