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Growth Inhibition of Glioma Cells Transfected with the Human ß-Interferon Gene by Liposomes Coupled with a Monoclonal Antibody¹

Department of Neurosurgery, Nagoya University School of Medicine, Nagoya 466 [M. M., J. Y., K. S., I. I.], Department of Endocrinology and Metabolism, Research Institute of Environmental Medicine, Nagoya University, Nagoya 464 [I. I., H. S.], and Institute of Applied Biochemistry, Yagi Memorial Park, Mitake, Gifu 505-01 [Y. H., T. K., K. Y.], Japan

A human ß-interferon (HuIFN-ß) gene inserted into a eukaryotic expression vector (pSV2IFN-ß) was entrapped in liposomes having positive charges on their surface. Liposome-mediated transfection of the gene into cultured glioma cells (U251-MG) resulted in the secretion of HuIFN-ß into the medium. The HuIFN-ß level in the culture medium of glioma cells reached 24 ± 8 (mean ± SD) IU/ml after 96 h of incubation, at which level the growth inhibitory effect on the cells was found to be >40 times as compared with exogenously added HuIFN-ß. When the plasmid-containing liposomes were coupled with a monoclonal antibody (G-22 MCA) against glioma-associated antigen, the level of HuIFN-ß in the medium was 178 ± 26 IU/ml, resulting in a 7-fold increase, and the growth inhibitory effect was further elevated. Since the addition of a monoclonal antibody against HuIFN-ß to the medium did not cause the cell growth to resume, the growth inhibitory effect on the cells seems to be ascribed to HuIFN-ß produced in the cells transfected with its gene. Accordingly, the specific delivery of the HuIFN-ß gene into glioma cells by the use of such liposomes might become a useful technique for gene therapy of malignant glioma.

¹ Supported in part by a Grant-in-Aid for New Drug Development from the Ministry of Health and Welfare of Japan.

² To whom reprint requests should be addressed.

Received 1/11/90. Accepted 8/31/90.

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