Tumor growth suppression by a retroviral vector displaying scFv antibody to CEA and carrying the iNOS gene.
BACKGROUND
In a recent in vitro study we demonstrated a specifically-targeted killing of CEA-expressing cells by a recombinant bifunctional retrovector displaying an scFv antibody to CEA and carrying the iNOS gene. In this study, we tested whether a gene therapy using the recombinant retrovirus could inhibit the growth of CEA-expressing tumors in mice.


METHODS
SCID mice were inoculated s.c. on the back with CEA-expressing MKN-45 cells on day 0. The recombinant viral particles were injected into the inoculated sites on days 3, 5 and 7 and tumor size was measured every 5 days.


RESULTS
The s.c. administration of the recombinant retrovirus produced a marked growth inhibition of MKN-45 tumors in SCID mice. When the actual tumor weights were measured 50 days after initiation of treatment, about 70% reduction was observed in the treated group as compared to the control groups.


CONCLUSIONS
This approach may also be applied to other tumor antigens expressed on cancer cells and is a step towards the cell specific suppression of tumorigenicity.
Khare
Pranay D
PD
First Department of Biochemistry, Fukuoka University School of Medicine, Japan.
Liao
Shaoxi
S
Hirose
Yumiko
Y
Kuroki
Motomu
M
Fujimura
Satoshi
S
Yamauchi
Yasushi
Y
Miyajima-Uchida
Hiroko
H
Kuroki
Masahide
M
D000818:Animals; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D051379:Mice; D016513:Mice, SCID; D019001:Nitric Oxide Synthase / Q000235:genetics*; D052247:Nitric Oxide Synthase Type II; D012190:Retroviridae; D013274:Stomach Neoplasms / Q000628:therapy*; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D002272:Carcinoembryonic Antigen; D007135:Immunoglobulin Variable Region; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse