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Significant Antitumoral Activity of Cationic Multilamellar Liposomes Containing Human IFN-ß Gene against Human Renal Cell Carcinoma¹

Department of Urology [H. N., Y. M., A. K., O. U., T. S., T. M.], Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan, and Departments of Molecular Neurosurgery [M. M.] and Neurosurgery [M. H., J. Y.], Nagoya University, Postgraduate School of Medicine, Nagoya 466-8550, Japan

Purpose: Immunotherapy is the most effective treatment against metastatic renal cell carcinoma (RCC). However, the response rate is 15%. More effective therapy is, therefore, needed for patients with metastatic RCC. We then examined the antitumor effect of cationic multilamellar liposome containing human IFN-ß (huIFN-ß) gene (IAB-1) against RCC.

Experimental Design: Concentrations of huIFN-ß protein were measured by ELISA. The cytotoxicity of IAB-1 against human RCC (NC65, ACHN, and freshly isolated RCC cells), prostate and bladder cancer cell lines, and renal proximal tubule endothelial cells (RPTEC5899) was examined by the colorimetric method using tetrazolium salt. Apoptosis was assessed by the acridine-orange staining. For in vivo study, we used NC65 cells inoculated into severe combined immunodeficiency mouse.

Results: The RCC cells treated with IAB-1 secreted significant amounts of huIFN-ß protein continuously. Drastic in vitro cytotoxic effect of IAB-1 against RCC was observed. In contrast, treatment with 1000 IU/ml recombinant huIFN-ß protein resulted in weak cytotoxicity. The cytotoxic effect against prostate and bladder cancer cell lines was less than that against RCC. Furthermore, no significant cytotoxicity was observed in RPTEC5899 cells. Apoptosis was observed in the cells treated with IAB-1, but recombinant huIFN-ß failed to induce apoptosis. The size of NC65 tumors transfected with IAB-1 in mice was significantly smaller than that receiving injection of empty liposome or recombinant huIFN-ß protein.

Conclusion: These findings indicate that IAB-1 may have an antitumor activity against human RCC by inducing apoptosis, suggesting its potential clinical application for gene therapy against RCC.

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