Lee C T, Wu S, Ciernik I F, Chen H, Nadaf-Rahrov S, Gabrilovich D, Carbone D P
Vanderbilt Cancer Center, Venderbilt University School of Medicine, Nashville, TN 37232-6838, USA.
Hum Gene Ther. 1997 Jan 20;8(2):187-93. doi: 10.1089/hum.1997.8.2-187.
Increased local production of granulocyte-macrophage colony-stimulating factor (GM-CSF) by genetically modified tumor cells can induce specific antitumor cellular immunity. We constructed a recombinant adenovirus expressing murine GM-CSF and tested it for therapeutic efficacy in a syngeneic murine lung cancer model system. In vitro transduction of Lewis lung carcinoma cells with adenovirus-mGM-CSF suppressed tumor formation in syngenic mice (C57BL/6), and transduced and irradiated Lewis lung carcinoma cells induced regression of pre-established wild-type tumors without in vitro selection for transductants. Low, but significant, levels of specific antitumor cytotoxic T lymphocytes (CTL) were observed in mice inoculated with GM-CSF but not with reporter virus-transduced tumor cells. GM-CSF-transduced cells induced the accumulation of dendritic cells at the site of tumor, consistent with a mechanism involving improved tumor antigen presentation. These data suggest that transduction of tumor cells with recombinant GM-CSF adenovirus may be an effective and practical cancer gene therapeutic strategy.
通过基因改造的肿瘤细胞增加粒细胞-巨噬细胞集落刺激因子（GM-CSF）的局部产生可诱导特异性抗肿瘤细胞免疫。我们构建了一种表达小鼠GM-CSF的重组腺病毒，并在同基因小鼠肺癌模型系统中测试其治疗效果。用腺病毒-mGM-CSF体外转导Lewis肺癌细胞可抑制同基因小鼠（C57BL/6）中的肿瘤形成，并且转导并照射的Lewis肺癌细胞可诱导预先建立的野生型肿瘤消退，而无需对转导子进行体外选择。在接种GM-CSF而非报告病毒转导的肿瘤细胞的小鼠中观察到低但显著水平的特异性抗肿瘤细胞毒性T淋巴细胞（CTL）。GM-CSF转导的细胞诱导树突状细胞在肿瘤部位积聚，这与涉及改善肿瘤抗原呈递的机制一致。这些数据表明，用重组GM-CSF腺病毒转导肿瘤细胞可能是一种有效且实用的癌症基因治疗策略。
