Lee, Sang-JinZhang, YanpingLee, Sang DonJung, ChaeyongLi, XiongKim, Hong-SupBae, Kyung-HeeJeng, Meei-HueyKao, ChinghaiGardner, Thomas2022-09-152022-09-152004-12-01Lee, S.-J., Zhang, Y., Lee, S. D., Jung, C., Li, X., Kim, H.-S., Bae, K.-H., Jeng, M.-H., Kao, C., & Gardner, T. (2004). Targeting Prostate Cancer with Conditionally Replicative Adenovirus Using PSMA Enhancer. Molecular Therapy, 10(6), 1051–1058. https://doi.org/10.1016/j.ymthe.2004.08.0281525-0016https://hdl.handle.net/1805/30013Prostate cancer is the second most commonly diagnosed cancer in men and accounts for significant mortality and morbidity in the United States. Initially androgen-dependent, prostate cancer ultimately becomes androgen-independent, which makes the disease extremely difficult to cure. In this study, we examined the use of conditionally replication-competent adenovirus for the treatment of hormone-independent prostate cancer. We utilized PSME, an enhancer element for prostate-specific PSMA expression, to control viral E1A protein expression and achieve exclusive virus replication in prostate. Western blotting confirmed that PSME mediated high E1A protein expression in PSMA-positive, androgen-independent prostate cancer cells (C4-2 and CWR22rv), but was much less active in PSMA-negative cancer cells (PC-3 and A549). Consistent with E1A protein expression, the recombinant adenovirus Ad5-PSME-E1a replicated in C4-2 and CWR22rv almost as efficiently as wild type with low levels of androgen, but its replication was significantly attenuated in PSMA-negative cells. In the in vitro killing assay, Ad5-PSME-E1a lysed all C4-2 and CWR22rv cells 5 days after infection, with minimal effect on PSMA-negative cells. In addition, injections of 1.7 × 108 plaque-forming units in a CWR22rv xenograft model in nude mice induced significant tumor growth delay, with a substantial necrotic area. These studies suggest that PSME-driven replication-competent adenovirus may be a new therapeutic modality for prostate cancer patients after hormone ablation therapy.enAttribution-NonCommercial-NoDerivatives 4.0 InternationalProstate Cancercancer treatmentandrogen-dependent prostate cancerArticle