Abstract 4412: Combining cytokine gene therapy with conventional cancer chemotherapyfor treatment of metastatic renal cell carcinoma

Abstract

Abstract Renal cell carcinoma (RCC) accounts for approximately 3% of adult malignancies and 85-90% of kidney cancer. Treatment was generally aggressive involving nephrectomy and excision of the metastatic lesion. The current study was designed to evaluate a new strategy for treatment of RCC, using combination of cytokine gene therapy with conventional cancer chemotherapy. The study established tumor metastasis in Balb/c mice using Renca cells as a model1. Treatment was performed on tumor bearing mice with hydrodynamic gene delivery of plasmids containing either mIL-2 or mIL-12 gene, separately, or in combination with or without two weekly injection of 5-flououracil (5-FU) (20 mg/kg, ip). The results showed that the lung, liver and kidney were the primary sites of tumor growth. 5-FU is capable of inhibiting tumor growth in the liver and kidney and effective in slowing down tumor growth in the lung when treatment started early and with high frequency. mIL-2 gene therapy inhibited tumor growth in the liver and kidney. The effect became more obvious if treatment started early. However, IL-2 alone is unable to eliminate all liver tumors. mIL-2 gene therapy had almost no effect on tumor growth in lung. mIL-12 gene therapy significantly blocked cancer-induced weight loss. mIL-12 inhibited tumor growth in the liver and kidney, but IL-12 alone is unable to eliminate all liver and kidney tumors. In addition, IL-12 inhibited lung swelling induced by tumor, especially when treatment was started early. Cytokine gene therapy combined with chemotherapy is effective in blocking tumor-induced weight loss, and tumor growth in the liver, lung and kidney. These results provide direct evidence in support that combined therapy of cytokine gene therapy with traditional chemotherapy is effective in treating RCC. Key words: Renal cell carcinoma, gene therapy, IL-12, IL-2, 5- flououracil 1 Jianfeng Li, Qian Yao and Dexi Liu (2011) Hydrodynamic cell delivery for simultaneous establishment of tumor growth in mouse lung, liver and kidney. Cancer Biol Ther 12:737-741. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4412. doi:1538-7445.AM2012-4412