High cytokine production and effective antitumor activity of a recombinant vaccinia virus encoding murine interleukin 12.
High cytokine production and effective antitumor activity of a recombinant vaccinia virus encoding murine interleukin 12.
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发表时间：
1995-11
期刊：
影响因子：
11.2
通讯作者：
J. Meko;J. Yim;K. Tsung;J. Norton
中科院分区：
文献类型：
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作者：
J. Meko;J. Yim;K. Tsung;J. Norton
我们构建了重组牛痘病毒 (recVV) vKT0334 mIL-12，其中含有编码鼠白细胞介素 12 (mIL-12) p35 和 p40 亚基的基因。体外实验表明，vKT0334 mIL-12 有效感染多种小鼠和人类肿瘤细胞系，并产生非常大量（1.5 微克/10(6) 细胞/24 小时）的具有生物活性的 mIL-12。小鼠皮下注射用 10(6) 个 MCA 105 肉瘤细胞，然后在同一部位注射盐水或不含 mIL-12 基因的对照 recVV、vKT033，所有动物均出现逐渐生长的肿瘤，而注射 vKT0334 mIL-12 的动物中有 60% 保持无肿瘤状态（P < 0.0005）。此外，与用 vKT033 (P < 0.03) 或盐水 (P < 0.0001) 治疗的小鼠相比，用 vKT0334 mIL-12 治疗的剩余小鼠中确实形成肿瘤的肿瘤生长显着减少。我们得出结论，表达高水平mIL-12的recVV提供了一种有效的体内细胞因子基因递送和肿瘤表达方法，并具有随后的抗肿瘤作用。
We have constructed a recombinant vaccinia virus (recVV), vKT0334 mIL-12, containing the genes encoding the p35 and p40 subunits of murine interleukin-12 (mIL-12). In vitro experiments demonstrated that vKT0334 mIL-12 efficiently infected a variety of murine and human tumor cell lines and produced very high amounts (1.5 micrograms/10(6) cells/24 h) of biologically active mIL-12. Mice injected s.c. with 10(6) MCA 105 sarcoma cells, followed by injection at the same site with saline or a control recVV, vKT033, containing no mIL-12 genes, all developed progressively growing tumor, whereas 60% of animals injected with vKT0334 mIL-12 remained tumor free (P < 0.0005). Furthermore, tumor growth was significantly reduced in the remaining mice treated with vKT0334 mIL-12 that did develop tumor compared with mice treated with vKT033 (P < 0.03) or saline (P < 0.0001). We conclude that recVV expressing high levels of mIL-12 offers an effective in vivo method of cytokine gene delivery and expression in tumors with subsequent antitumor effect.