Adenovirus-mediated murine interferon-gamma receptor transfer enhances the efficacy of IFN-gamma in vivo.
Interferon gamma (IFN-gamma) plays an important role in immune response, apoptosis, and anti-tumor activity. Its biological activity depends on expression of IFN-gamma receptor (IFN-gammaR). To address whether increased expression of IFN-gammaR is associated in vivo with a higher biological response by IFN-gamma, we constructed an adenovirus vector including murine IFN-gammaR (Ad-mIFN-gammaR). We confirmed the appropriate function of mIFN-gammaR derived from Ad-mIFN-gammaR based on the observation of signal transduction and transcription. We also found that elevated expression of mIFN-gammaR increases sensitivity to recombinant murine IFN-gamma (rmIFN-gamma) in vitro in target cells. Furthermore, we demonstrated that the growth rate of tumors transfected with Ad-mIFN-gammaR is suppressed in response to rmIFN-gamma in vivo and that such growth suppression is partly due to apoptosis. To our knowledge, this is the first report of adenovirus-mediated IFN-gammaR gene transfer being effective in augmenting the biological activity of IFN-gamma, and the strategy employed in the present study will be useful in studying other kinds of cytokine receptors and applications to gene therapy for cancer and infectious diseases.
Nishida
Yasuto
Y
Department of Neurology, Kumamoto University, School of Medicine, 1-1-1 Honjo, Kumamoto, Kumamoto, 860-0811, Japan.
Maeda
Yasushi
Y
Hara
Akio
A
Arima
Toshiyuki
T
Kimura
En
E
Yamashita
Satoshi
S
Uyama
Eiichiro
E
Mita
Shuji
S
Uchino
Makoto
M
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D002455:Cell Division; D002460:Cell Line; D054357:Chemokine CXCL10; D019743:Chemokines, CXC / Q000096:biosynthesis / Q000235:genetics; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D050832:Interferon-Stimulated Gene Factor 3; D007371:Interferon-gamma / Q000494:pharmacology*; D051379:Mice; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology / Q000628:therapy*; D012333:RNA, Messenger / Q000096:biosynthesis; D017471:Receptors, Interferon / Q000235:genetics*; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured; D000096743:Interferon gamma Receptor
D000970:Antineoplastic Agents; D054357:Chemokine CXCL10; D019743:Chemokines, CXC; D050832:Interferon-Stimulated Gene Factor 3; D007371:Interferon-gamma; D012333:RNA, Messenger; D017471:Receptors, Interferon; D014157:Transcription Factors; D000096743:Interferon gamma Receptor; C079868:gamma interferon activation factor