title: Therapeutic efficacy of an oncolytic adenovirus containing RGD ligand in minor capsid protein IX and Fiber, Δ24DoubleRGD, in an ovarian cancer model.
abstract: Ovarian cancer is the leading cause of gynecological disease death despite advances in medicine. Therefore, novel strategies are required for ovarian cancer therapy. Conditionally replicative adenoviruses (CRAds), genetically modified as anti-cancer therapeutics, are one of the most attractive candidate agents for cancer therapy. However, a paucity of coxsackie B virus and adenovirus receptor (CAR) expression on the surface of ovarian cancer cells has impeded treatment of ovarian cancer using this approach. This study sought to engineer a CRAd with enhanced oncolytic ability in ovarian cancer cells, "Δ24DoubleRGD." Δ24DoubleRGD carries an arginine-glycine-aspartate (RGD) motif incorporated into both fiber and capsid protein IX (pIX) and its oncolytic efficacy was evaluated in ovarian cancer.In vitroanalysis of cell viability showed that infection of ovarian cancer cells with Δ24DoubleRGD leads to increased cell killing relative to the control CRAds. Data from this study suggested that not only an increase in number of RGD motifs on the CRAd capsid, but also a change in the repertoir of targeted integrins could lead to enhanced oncolytic potency of Δ24DoubleRGD in ovarian cancer cellsin vitro. In an intraperitoneal model of ovarian cancer, mice injected with Δ24DoubleRGD showed, however, a similar survival rate as mice treated with control CRAds.
authors.affiliation: Division of Human Gene Therapy, Departments of Medicine, Pathology, Surgery, Obstetrics and Gynecology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA ; University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
authors.forename: Lena J
authors.initials: LJ
authors.lastname: Gamble
authors.forename: Hideyo
authors.initials: H
authors.lastname: Ugai
authors.forename: Minghui
authors.initials: M
authors.lastname: Wang
authors.forename: Anton V
authors.initials: AV
authors.lastname: Borovjagin
authors.forename: Qiana L
authors.initials: QL
authors.lastname: Matthews
keywords: Conditionally replicative adenoviruses (CRAds); anti-cancer therapy; arginine-glycine-aspartate (RGD) motif; capsid-modification; ovarian cancer