Tsuji Hideki, Kawaguchi Satoshi, Wada Takuro, Nagoya Satoshi, Inobe Manabu, Yagita Hideo, Okumura Ko, Yamashita Toshihiko, Uede Toshimitsu
Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine, Sapporo, Japan.
Cancer Gene Ther. 2003 Sep;10(9):717-25. doi: 10.1038/sj.cgt.7700624.
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.
为建立一种有效的基于B7的骨肉瘤基因治疗方法，我们通过腺病毒将B7-1/Fas嵌合基因导入免疫原性较差的骨肉瘤细胞。我们发现，腺病毒介导的大鼠B7-1/Fas基因转移可诱导：（i）骨肉瘤细胞中大鼠B7-1/Fas嵌合分子的表达；（ii）小鼠T细胞的激活；（iii）在体外抗大鼠B7-1单克隆抗体存在的情况下小鼠骨肉瘤细胞的凋亡；以及（iv）比B7-1基因转移对小鼠肺转移的发展和生存具有更显著的治疗效果。这些发现共同支持了腺病毒介导的B7-1/Fas基因转移对免疫原性较差的骨肉瘤的治疗价值，这种骨肉瘤对仅使用B7-1转导的治疗方案具有抗性。
