Growth inhibition of glioma cells transfected with the human beta-interferon gene by liposomes coupled with a monoclonal antibody.
A human beta-interferon (HuIFN-beta) gene inserted into a eukaryotic expression vector (pSV2IFN-beta) 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-beta into the medium. The HuIFN-beta 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 greater than 40 times as compared with exogenously added HuIFN-beta. When the plasmid-containing liposomes were coupled with a monoclonal antibody (G-22 MCA) against glioma-associated antigen, the level of HuIFN-beta 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-beta to the medium did not cause the cell growth to resume, the growth inhibitory effect on the cells seems to be ascribed to HuIFN-beta produced in the cells transfected with its gene. Accordingly, the specific delivery of the HuIFN-beta gene into glioma cells by the use of such liposomes might become a useful technique for gene therapy of malignant glioma.
Mizuno
M
M
Department of Neurosurgery, Nagoya University School of Medicine, Japan.
Yoshida
J
J
Sugita
K
K
Inoue
I
I
Seo
H
H
Hayashi
Y
Y
Koshizaka
T
T
Yagi
K
K
D000818:Animals; D000911:Antibodies, Monoclonal; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D005822:Genetic Vectors; D005910:Glioma / Q000473:pathology*; D006801:Humans; D007370:Interferon Type I / Q000235:genetics* / Q000494:pharmacology / Q000502:physiology; D008081:Liposomes; D010957:Plasmids; D013539:Simian virus 40 / Q000235:genetics; D014162:Transfection
D000911:Antibodies, Monoclonal; D007370:Interferon Type I; D008081:Liposomes