544. Interferon alpha-2b Gene Delivery for Bladder Cancer Demonstrates Feasibility of Repeated Intravesical Dosing with an Adenovirus Vector

Abstract

Intravesical interferon protein therapy has been utilized as a monotherapy for treatment of superficial bladder cancer with only modest success, likely in part due to the limited exposure of bladder tumors to interferon. To increase exposure of the bladder tumors to interferon, we have utilized an adenoviral delivery system (rAd) to deliver and express the human secreted interferon alpha-2b gene product (rAd-IFN) using a novel polyamide (Syn3) formulation that dramatically enhanced the uptake and expression of adenoviral vectors in the normal urothelium (Connor et al., 2001) and tumor tissue (Yamashita et al., 2002). We evaluated whether rAd-IFN could improve the tissue and urine levels of interferon protein by transducing the urothelium with the secreted human interferon-alpha gene (IFN alpha). We also assessed the possibility of repeated intravesical dosing with an adenovirus vector to mimic clinical need of multiple dosing cycles for cancer therapies.