INTRODUCTION AND OBJECTIVE: Renal Cell Carcinoma (RCC) is the third most common urologic neoplasm. Radiation and chemotherapy have largely proven ineffective in treating metastatic disease. Immunotherapy has shown modest results. These limitations have prompted investigation into novel techniques. One promising area is gene therapy. The highly vascular tumors of RCC appear to be highly susceptible to antiangiogenic gene therapy. The aim of this study was to produce metastatic tumor inhibition using combined treatments of tailored adenovirus therapy.

METHODS: Subcutaneous RCC-29 tumors were induced in 7-week old athymic nude male mice by injecting 2x106 cells bilaterally into each flank region. On days 2 and 10 post-injection, the mice were subjected to an intratumoral injection of adenoviral vector on the right flank only. The mice were randomly assigned to seven treatment groups: control (n=7), GFP (n=7), Tie2 (n=9), Endostatin/Angiostatin (n=8), GFP + Tie2 (n=7), GFP + EndoAngio (n=9), and EndoAngio + Tie2 (n=8). Each group received two injections of 2x109 PFU respectively. The tumor volumes were measured twice weekly for 60 days. Additionally, during days 40-50 of the trial, the subjects were administered fluorescent rhodamine-conjugated BSA dye and skin windows were established over the tumors. Using dual-photon optical imaging, qualitative assessment of tumor vasculature was performed.

RESULTS: Tumors treated with adenovirus expressing endostatin-angiostatin fusion protein, GFP + EndoAngio, and EndoAngio + Tie2 demonstrated 82%, 83%, and 87% growth reduction respectively (p<0.001) as compared to controls. Further, in vivo imaging illustrated a reduction in blood vessel number and size in the EndoAngio treatment groups as compared to controls.

CONCLUSIONS: These results suggest that adenoviral vectors expressing Endostatin/Angiostatin fusion proteins have effective antiangiogenic action against human RCC cells and possess great potential as a novel treatment for metastatic renal cell carcinoma.

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA