Gene therapy of renal cancer using recombinant adeno-associated virus encoding human endostatin.

Abstract

Renal cell carcinoma (RCC) is characterized by robust angiogenesis during tumor development. Various therapies are not able completely eradicated tumor relapse. The present study targeted angiogenesis and developed a recombinant adeno-associated virus (rAAV) vector containing human endostatin gene for human kidney cancer gene therapy. Prophylactic and therapeutic RCC models were established in nude mice by subcutaneous inoculation of RCC cells and intra-muscular or intra-tumor injection of rAAV-Endostatin. The growth of xenograft tumors was evaluated by tumor volume and weight. The microvessel density (MVD) was used to measure the anti-angiogenesis effect of rAAV-Endostatin. The toxic effect of rAAV-Endostatin was also examined. In the therapeutic model, tumor-bearing mice with rAAV-Endostatin intra-tumor injection demonstrated slow tumor growth (32.63±9.75) compared with control groups with intratumoral rAAV-enhanced yellow florescent protein (EYFP) injections (21.50±11.42) and the RPMI-1640 group (21.75±10.48 days, for tumors to reach ~300 mm3). MVD of the xenografts treated with rAAV-Endostatin was 8.30±3.14/0.739 mm2 whereas that of control groups was 13.87±4.09/0.739 mm2 (rAVV-EYFP) and 13.76±3.50/0.739 mm2 (RPMI-1640). No significant side effects associated with rAAV-endostatin use were identified in the vital organs. rAAV-Endostatin demonstrated significant anti-angiogenesis and antitumor activities. It may serve as an effective agent for renal cancer gene therapy.