Vascular endothelial growth factor promoter ‐based conditionally replicative adenoviruses effectively suppress growth of malignant pleural mesothelioma

In this study, we investigated the effectiveness of the intrapleural instillation of a replication‐competent adenovirus as an oncolytic agent against MPM. We constructed a vascular endothelial growth factor promoter‐based conditionally replicative adenovirus (VEGF‐CRAd) that replicates exclusively in VEGF‐expressing cells. All of the MM cell lines that we tested expressed VEGF mRNA, and VEGF‐CRAd selectively replicated in these MM cells and exerted a direct concentration‐dependent oncolytic effect in vitro. Furthermore, our in vivo studies showed that pre‐infection of MM cells with VEGF‐CRAd potently suppressed MPM tumor formation in nude mice, and that intrapleural instillation of VEGF‐CRAd prolonged the survival time of tumor‐bearing mice. Our results indicate that VEGF‐CRAd exerts an oncolytic effect on MM cells and that intrapleural instillation of VEGF‐CRAd is safe and might represent a promising therapeutic strategy for MPM. Vascular endothelial growth factor plays a pivotal role and is a potential target molecule for new MM therapies. VEGF‐CRAd produces oncolytic effects in MM in vitro. VEGF‐CRAd offers survival benefits in MPM tumor‐bearing mice.
Source: Cancer Science - Category: Cancer & Oncology Authors: Tags: Original Article Source Type: research