Antitumor and antiangiogenic effects of interleukin 12 gene therapy in murine head and neck carcinoma model.
Interleukin-12 (IL-12) plays a critical role in producing an immune response, as indicated in many ways, e.g., induction of interferon-gamma (IFN-gamma), and augmentation of the cytotoxic activity of resting activated T cells and natural killer (NK) cells. In this study, we examined whether intratumoral injection of a recombinant retrovirus vector expressing IL-12s induce antitumor and antiangiogenic effects in a murine model using a murine head and neck squamous cell carcinoma (NR-S1). In vitro the levels of vascular endothelial growth factor (VEGF) mRNA and protein expression were decreased in IL-12 gene transfected NR-S1 cell. in vivo direct IL-12 gene therapy resulted in significantly remarkable inhibition of tumor growth compared to the control group. The tumor regression by direct IL-12 gene therapy was also associated with decreased vessel density, and apoptosis and increased infiltration of CD8(+) T cells and CD56(+) NK cells in the tumor increased. Also, the number of IFN-gamma expressed cells of spleen cells was increased in the treatment group compared with the control group. These results suggested that direct IL-12 gene therapy appears to be effective in reducing tumor growth by triggering both antiangiogenic effects and an immunological enhancing mechanism through induction of IFN-gamma.
Imagawa
Yukari
Y
Department of Biology and Function in the Head and Neck, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan. yanca@med.yokohama-cu.ac.jp
Satake
Kenichi
K
Kato
Yasumasa
Y
Tahara
Hideaki
H
Tsukuda
Mamoru
M
D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D019002:CD56 Antigen / Q000187:drug effects / Q000276:immunology; D016827:CD8 Antigens / Q000187:drug effects / Q000276:immunology; D002294:Carcinoma, Squamous Cell / Q000737:chemistry / Q000276:immunology / Q000628:therapy*; D002452:Cell Count; D045744:Cell Line, Tumor; D015316:Genetic Therapy / Q000379:methods*; D006258:Head and Neck Neoplasms / Q000737:chemistry / Q000276:immunology / Q000628:therapy*; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007267:Injections; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D018664:Interleukin-12 / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D007694:Killer Cells, Natural / Q000378:metabolism; D016246:Lymphocytes, Tumor-Infiltrating / Q000737:chemistry; D051379:Mice; D012333:RNA, Messenger / Q000187:drug effects; D014162:Transfection / Q000379:methods; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D019002:CD56 Antigen; D016827:CD8 Antigens; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D018664:Interleukin-12; D007371:Interferon-gamma