Dual-Action Armed Replicating Adenovirus for the Treatment of Osteoblastic Bone Metastases of Prostate Cancer.

摘要

We hypothesize that the efficacy of a replicating adenovirus for the treatment of bone metastases of prostate cancer could be enhanced by arming it with the therapeutic protein sOPG-Fc which will block osteoclastic bone resorption and hence inhibit bone remodeling. Thus we constructed a dual-action armed replicating adenovirus expressing sOPG-Fc designed to both directly kill metastatic prostate cancer cells by oncolysis and also secrete sOPG-Fc into the microenvironment of the bone thereby inhibiting osteoclastic bone resorption. We have shown that the sOPG-Fc gene is expressed in a similar temporal manner to the E3B genes which it replaced and that the remaining E3 genes continue to be expressed. We have confirmed that expression of sOPG-Fc does not impair the selectivity or oncolytic potency of the armed replication-selective adenovirus. We have confirmed that the armed replicating adenovirus can simultaneously eradicate prostate cancer cells by oncolysis and inhibit osteoclast formation in vitro.