K. Yagi et al., Basic study on gene therapy of human malignant glioma by use of the cationic multilamellar liposome-entrapped human interferon beta gene, HUM GENE TH, 10(12), 1999, pp. 1975-1982
For gene therapy of human malignant glioma, we adopted positively charged m
ultilamellar liposomes entrapping the human interferon beta (hIFN-beta) gen
e. One week after the transplantation of human malignant glioma U251-SP cel
ls to produce glioma in nude mouse brain, the liposomes entrapping the gene
(500 ng of DNA per 25 nmol of lipids per 2 mu l) were injected into the sa
me site of the cell transplantation once every second day for a total of fi
ve injections; and by this means the tumor completely disappeared. To confi
rm the antiproliferative effect of hIFN-beta, we performed an in vitro stud
y using a plasmid containing a secretion signal sequence-deleted hIFN-beta
gene and one containing the hIFN-beta gene inserted in reverse. In both cas
es, there was no hIFN-beta release into the medium and no growth inhibition
effect. On addition of anti-hIFN-beta antibody to the medium, the growth i
nhibition effect was abolished. As this cell line expresses IFN-alpha/beta
receptor, the hIFN-beta produced in the transfected cells could be released
and acted in a paracrine manner. For 120 days the body weight change of no
rmal mice treated by the same procedure as used in the curing experiment wa
s not significant among the groups injected with empty liposomes, plasmid o
nly, and liposomes entrapping the gene. In all of these three groups, death
, abnormal behavior, and significant histological changes were not observed
.