Therapeutic Potential Of Adenovirus Mediated Interleukin12 Gene Therapy For Prostate Cancer

Shin Ebara,1 Yasutomo Nasu,1 Takefumi Satoh,1 Satoru Shimura,1 Chris H. Bangma,1 Gerald W. Hull,1 Mark A. McCurdy,1 Jianxiang Wang,1 Guang Yang,1 Terry L. Timme,1 and Timothy C. Thompson1,2,3

Scott Department of Urology,1 Department of Molecular and Cellular Biology,2 and Department of Radiology,3 Baylor College of Medicine, Houston, Texas, USA

Key words: Interleukin-12; prostate cancer; orthotopic prostate cancer model; in situ gene therapy; metastasis

Abstract: Prostate cancer is characterized by extreme heterogeneity and multifocality of the primary tumour. The available clinical, pathological and molecular data suggest a lack of substantial clonal expansion at the primary site, yet metastatic progression of the disease often proceeds in an unpredictable and clinically undetectable fashion. Clinical and experimental data suggest that primary prostate cancer tumour cells can seed from relatively small tumour foci at the primary site. Overall, this unique biological pattern of progression presents unique and challenging problems regarding the detection and treatment of the disease. In general, currently used potentially curative therapies involve a single cytoablative modality (radical prostatectomy or radiation therapy) and are exclusively directed at the malignant cells within the prostate gland. At present the widespread use of these treatments has not resulted in substantial reduction in mortality from prostate cancer. Gene therapy used alone or as an adjuvant approach could, at least conceptually, provide a rational solution for the prostate cancer dilemma. With gene therapy protocols designed to stimulate antitumour immunity, it may be possible to treat localized and systemic disease effectively and simultaneously. Our previous preclinical and clinical studies have focused on the use of adenoviral vector-mediated 1 (SV-.'i ■ (Herpes Simplex Virus thymidine kinase + ganciclovir) in situ gene therapy for prostate cancer. More

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