295. Effects of Sustained Anti-Angiogenic Gene Therapy in Multi-Stage Prostate Cancer in TRAMP Mice

Abstract

Anti-angiogenic gene therapy is a rational alternative for inhibiting tumor growth and metastasis and holds greater promise as an adjuvant therapy. Since this form of therapy targets tumor vasculature and not tumor cells directly, for sustained tumoristatic effects, stable expression of anti-angiogenic factors at a therapeutic level needs to be maintained. In the present study, we evaluated the potential of recombinant adeno-associated virus (rAAV)-mediated stable expression of angiostatin and endostatin during early and late stages of prostate cancer progression in TRAMP mice. Cohorts of 8 week- old and 18 week-old male TRAMP mice received either no virus or 1.2 |[times]| 1011 genomic particles of rAAV encoding green fluorescent protein (GFP) or mouse endostatin plus angiostatin by intramuscular (i.m.) injection. The effects of therapy were determined by periodic immunohistochemical analyses of the prostate for apoptotic index, endothelial cell growth and tumor proliferation. The levels of endostatin and angiostatin in systemic circulation were measured by ELISA and survival index was recorded as the endpoint.