Concurrent induction of T-cell activation and apoptosis of osteosarcoma cells by adenovirus-mediated B7-1/Fas chimeric gene transfer.
To establish an effective B7-based gene therapy against osteosarcoma, we transferred B7-1/Fas chimeric gene adenovirally into poorly immunogenic osteosarcoma cells. We found that adenovirus-mediated rat B7-1/Fas gene transfer induced (i) expression of rat B7-1/Fas chimeric molecules in osteosarcoma cells, (ii) activation of murine T cells, (iii) apoptosis of murine osteosarcoma cells in the presence of anti-rat B7-1 mAb in vitro, and (iv) therapeutic effects more prominently than B7-1 gene transfer on the development of pulmonary metastasis and survival of mice. These findings collectively support the therapeutic value of adenovirus-mediated B7-1/Fas gene transfer on poorly immunogenic osteosarcoma, which is resistant to a treatment protocol using transduction of B7-1 alone.
Tsuji
Hideki
H
Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine, Sapporo, Japan.
Kawaguchi
Satoshi
S
Wada
Takuro
T
Nagoya
Satoshi
S
Inobe
Manabu
M
Yagita
Hideo
H
Okumura
Ko
K
Yamashita
Toshihiko
T
Uede
Toshimitsu
T
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D017209:Apoptosis; D018122:B7-1 Antigen / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics; D007167:Immunotherapy; D008213:Lymphocyte Activation; D051379:Mice; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy; D012516:Osteosarcoma / Q000235:genetics* / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D051381:Rats; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism* / Q000627:therapeutic use
D018122:B7-1 Antigen; D019014:fas Receptor