Antitumor effects of interferon-omega: in vivo therapy of human tumor xenografts in nude mice.
The antitumor effect of the type I IFN, IFN-omega, was evaluated in both in vitro and in vivo studies of human cancer. For these studies, the cDNA for human IFN-omega was cloned into a eukaryotic expression plasmid DNA (pDNA) driven by the cytomegalovirus promoter. Supernatants from UM449 cells transfected in vitro with IFN-omega pDNA had antiproliferative effects on 11 of 13 human tumor cell lines. For in vivo studies, nude mice were implanted s.c. with one of the following human tumors: NIH: OVCAR-3 ovarian carcinoma, A375 melanoma, or A431 epidermoid carcinoma. Direct intratumoral injection of 100 microg of a IFN-omega pDNA DMRIE/DOPE complex (1:1 DNA:DMRIE mass ratio) for 6 consecutive days resulted in a significant reduction in the tumor volume of NIH: OVCAR-3 ovarian carcinoma or A375 melanoma (P = 0.02). IFN-omega pDNA delivered by i.m. injection also had an antitumor effect. Nude mice bearing s.c. A431 epidermoid carcinoma and injected i.m. with 100 microg of IFN-omega pDNA, twice per week for 3 weeks, had a significant reduction in tumor volume (P = 0.009). These results demonstrate for the first time that IFN-omega can have in vivo antitumor effects in several models of human cancer.
Horton
H M
HM
Vical, Inc., San Diego, California 92121, USA. hhorton@vical.com
Hernandez
P
P
Parker
S E
SE
Barnhart
K M
KM
D000818:Animals; D005260:Female; D006801:Humans; D007370:Interferon Type I / Q000008:administration & dosage* / Q000235:genetics; D008545:Melanoma / Q000188:drug therapy* / Q000235:genetics; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000235:genetics; D014162:Transfection; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D007370:Interferon Type I; C063743:interferon omega 1