A Dual-Action Armed Replicating Adenovirus for the Treatment of Osteoblastic Bone Metastases of Prostate Cancer
Annual rept. 31 Aug 2004-28 Feb 2006
ALABAMA UNIV IN BIRMINGHAM
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In this Exploration - Hypothesis Development Award 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 the objective of this proposal is to generate a dual-action armed replicating adenovirus which will both directly kill metastatic prostate cancer cells by oncolysis and will also secrete sOPG-Fc into the microenvironment of the bone thereby inhibiting osteoclastic bone resorption. To date we have constructed armed replication-selective adenoviruses expressing sOPG-Fc. We have confirmed 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 also confirmed that expression of sOPG-Fc does not impair the selectivity or oncolytic potency of the armed replication-selective adenovirus.
- Medicine and Medical Research