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 vitro analysis 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 cells in vitro. In an intraperitoneal model of
ovarian cancer, mice injected with Δ24DoubleRGD showed, however, a similar survival rate as mice treated with control CRAds.