Human and mouse IFN-beta gene therapy exhibits different anti-tumor mechanisms in mouse models.
Previously, we suggested that local human interferon-beta (IFN-beta) gene therapy with replication-defective adenoviral vectors can be an effective cancer treatment. Clinical trials to treat cancers with adenovirus expressing the human IFN-beta gene (IFNB1) has been planned. As a continued effort to explore the mechanisms of action of human IFN-beta gene therapy that can occur in the clinical setting, we tested mouse IFN-beta gene therapy in human xenograft tumors in both ex vivo and in vivo models. Delivery of the mouse IFN-beta gene (Ifnb) caused tumor inhibition; this effect was dependent on the indirect anti-tumor activities of IFN-beta, notably a stimulation of natural killer cells. IFN-beta does not show cross-species activity in its anti-proliferative effect and mouse IFN-beta does not cause as significant an anti-proliferative effect on mouse tumor cells as human IFN-beta causes on human tumor cells. Therefore, we believe that mouse models using either human IFN-beta or mouse IFN-beta gene transfer do not capture all aspects of the action of adenovirus-mediated human IFN-beta gene therapy that may be present in the clinical setting. Due to its multiple mechanisms of action, human IFN-beta gene therapy may be effective in treating human cancers that are either sensitive or resistant to the direct anti-proliferative effect of IFN-beta.
Qin
X Q
XQ
Biogen, Inc., 14 Cambridge Center, Cambridge, Massachusetts 02142, USA. xiao_qiang_qin@biogen.com
Beckham
C
C
Brown
J L
JL
Lukashev
M
M
Barsoum
J
J
D000256:Adenoviridae / Q000235:genetics / Q000502:physiology; D000818:Animals; D002455:Cell Division; D003602:Cytotoxicity, Immunologic; D004195:Disease Models, Animal; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics; D006801:Humans; D016899:Interferon-beta / Q000235:genetics* / Q000276:immunology / Q000627:therapeutic use*; D007694:Killer Cells, Natural / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis / Q000235:genetics / Q000473:pathology / Q000628:therapy; D009369:Neoplasms / Q000235:genetics / Q000276:immunology / Q000473:pathology* / Q000628:therapy*; D016019:Survival Analysis; D014183:Transplantation, Heterologous / Q000276:immunology / Q000473:pathology; D014407:Tumor Cells, Cultured
D016899:Interferon-beta