Abstract
We have previously reported that an osteosarcoma vaccine generated by ex vivo transfection of B7-1 cDNA induces protective as well as curative immunity against B7-1–negative parental osteosarcoma. Because establishment of human osteosarcoma cell lines, which is a prerequisite for ex vivo gene transfer, is rarely successful, we, in the present study, investigated the therapeutic efficacy of adenovirus-mediated in vivo B7-1 gene transfer to pre-established primary tumor as well as pulmonary metastasis of osteosarcoma. Adenovirus-mediated rat B7-1 gene transfer induced (a) expression of B7-1 molecules in osteosarcoma cells by both in vitro and in vivo infection procedures, (b) curative immunity against pre-established primary osteosarcoma and, subsequently, hosts gained protection against additional challenge of parental B7-1–negative osteosarcoma cells, (c) systemic immunity against pre-established pulmonary metastasis, and (d) activation of regional lymph node CD4+ T cells, expansion of dendritic cells and natural killer cells and the secretion of interferon-γ. These findings collectively support the therapeutic value of adenovirus-mediated in vivo gene transfer on osteosarcoma, which is of greater simplicity than cell-based B7-1 vaccine, and represent an attractive strategy for therapy of patients with metastatic osteosarcama who acquired resistance to current therapeutic protocols.
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Acknowledgements
We thank K Sato and K Takahashi (Department of Oral Surgery, Chiba University, Japan) for the kind donation of MSK-8G cells. We also thank M Kaya for technical assistance and Hideki Ito for taking microphotography of tumor sections. This study was supported by the Grant-in-Aid provided by the Ministry of Education, Science, Sports, and Culture of Japan (Grant 11307026).
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Tsuji, H., Kawaguchi, S., Wada, T. et al. Adenovirus-mediated in vivo B7-1 gene transfer induces anti–tumor immunity against pre-established primary tumor and pulmonary metastasis of rat osteosarcoma. Cancer Gene Ther 9, 747–755 (2002). https://doi.org/10.1038/sj.cgt.7700491
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DOI: https://doi.org/10.1038/sj.cgt.7700491
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