Adenovirus-Based Targeted Therapy for the Treatment of Endometriosis

Purpose: Endometriosis is a common gynecological disease associated with pain and infertility. Endoscopic surgery with removal of endometriotic lesions is regarded as the best therapeutic option. However, in patients with deep infiltrating endometriosis and/or recurrent disease, effective non-operative treatment alternatives are lacking. Thus, a specific targeted therapy would be a useful approach for a systemic therapy of endometriosis. This study aimed to evaluate potential molecular targets for a targeted therapy of endometriosis. Material and Methods: Immunostaining and gene expression analysis was performed to evaluate the expression of VEGF, Midkine, angiopoietin-2 and heparanase in eutopic endometrium, endometriotic lesions and normal peritoneum. The expression levels of VEGF and heparanase were evaluated in superficial endometriotic lesions and deep infiltrating endometriosis. A VEGF-targeted recombinant adenovirus (Ad5VEGFE1) was evaluated with regard to viral replication in endometriosis cells and induction of apoptosis. The biodistribution of the VEGF-targeted conditionally replicative adenovirus (CRAd) was examined in a mouse model. Results: VEGF and heparanase show specific expression in ectopic endometrium compared to eutopic endometrium and normal peritoneum. In addition, the corresponding promoters of both genes are active in endometriotic cells. A correlation between the promoter activity and the clinical stage of disease could only be demonstrated for the VEGF promoter. The recombinant conditionally replicative adenovirus Ad5VEGFE1 showed efficient induction of apoptosis in purified primary endometriotic cells in vitro and demonstrated comparable lower targeting to the liver and uterus in a mouse model. Conclusions: Ad5VEGFE1 is a promising candidate to treat endometriosis and exhibits potential for clinical testing.