Lentiviral interferon: A novel method for gene therapy in bladder cancer.

456Background: Gene therapy for bladder cancer (BLCA) is rapidly evolving. We reported that intravesical adenoviral interferon-alpha (Ad-IFNα) produced a complete response in 35% of patients with BCG-unresponsive BLCA enrolled in a Phase II trial. Lentivirus(LV) is another potential vector for intravesical delivery of IFNα. Unlike the adenovirus, LV can infect non- dividing cellsand integrate into the host’s genome, making it one of the most efficient gene deliveryvectors. The objective of this study was to investigate lentiviral interferon-alpha (LV-IFNα) BLCA gene therapy in preclinical models. Methods: Murine BLCA cell lines were transduced in-vitro with LV-IFNα using a multiplicityof infection(MOI) of 2:1. IFNα levelswere measuredby ELISA. Cell viability was assessed using Trypan bluedye exclusion. qPCR was used to identify expression of IFNα target genes. A LV-βGalactosidase reporter construct was delivered intravesically, and urinary IFNα levelswere measuredin mice treated with LV-IFNα or c...