Tumor growth suppression by a retroviral vector displaying scFv antibody to CEA and carrying the iNOS gene.

Tumor growth suppression by a retroviral vector displaying scFv antibody to CEA and carrying the iNOS gene.
复制标题

通过展示针对 CEA 的 scFv 抗体并携带 iNOS 基因的逆转录病毒载体抑制肿瘤生长。

DOI:
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发表时间:
2002
影响因子:
2
通讯作者:
M. Kuroki
M. Kuroki
中科院分区:
医学4区
文献类型:
--
作者:
P. Khare;S. Liao;Y. Hirose;M. Kuroki;S. Fujimura;Y. Yamauchi;H. Miyajima;M. Kuroki

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背景 在最近的一项体外研究中,我们展示了展示抗CEA单链抗体并携带iNOS基因的重组双功能逆转录载体对CEA表达细胞的特异性靶向杀伤作用。在这项研究中,我们测试了使用重组逆转录病毒的基因治疗是否可以抑制表达CEA的小鼠肿瘤的生长。 材料和方法 将SCID小鼠接种S.C.背面为第0天表达CEA的MKN-45细胞。于第3、5、7天将重组病毒颗粒注射到接种部位,每隔5天测量肿瘤大小。 结果 南卡罗来纳州重组逆转录病毒对SCID小鼠MKN-45肿瘤生长有明显的抑制作用。当在治疗开始后50天测量实际的肿瘤重量时,与对照组相比,治疗组观察到大约70%的减少。 结论 这种方法也可以应用于癌细胞上表达的其他肿瘤抗原,是朝着细胞特异性抑制致瘤性的方向迈出的一步。
BACKGROUND In a recent in vitro study we demonstrated a specifically-targeted killing of CEA-expressing cells by a recombinant bifunctional retrovector displaying an scFv antibody to CEA and carrying the iNOS gene. In this study, we tested whether a gene therapy using the recombinant retrovirus could inhibit the growth of CEA-expressing tumors in mice. MATERIALS AND METHODS SCID mice were inoculated s.c. on the back with CEA-expressing MKN-45 cells on day 0. The recombinant viral particles were injected into the inoculated sites on days 3, 5 and 7 and tumor size was measured every 5 days. RESULTS The s.c. administration of the recombinant retrovirus produced a marked growth inhibition of MKN-45 tumors in SCID mice. When the actual tumor weights were measured 50 days after initiation of treatment, about 70% reduction was observed in the treated group as compared to the control groups. CONCLUSION This approach may also be applied to other tumor antigens expressed on cancer cells and is a step towards the cell specific suppression of tumorigenicity.