摘要
目的:研究工程化抗体ATF-Fc对肿瘤生长和转移的影响。方法:构建由人尿激酶氨基端片段(ATF)和人IgG1的Fc片段连接而成的抗体样分子ATF-Fc,并用肿瘤细胞和裸鼠荷瘤动物模型评价其抗肿瘤生物活性。结果:ATF-Fc对多种肿瘤细胞系具有明显的杀伤作用,其杀伤作用与肿瘤细胞表达uPAR和分泌uPA水平密切相关。ATF-Fc能明显抑制在裸鼠皮下接种的人MCF-7乳腺癌和BGC-823胃癌的生长和肿瘤的肝转移,其对MCF-7和BGC-823肿瘤的抑制率分别为84%和74%,与对照组相比差异有统计学意义,P<0.001。结论:ATF-Fc是一个新的抗肿瘤抗体,其抗肿瘤作用通过干扰uPA/uPAR相互作用来实现。
OBJECTIVE：To investigate the effect of ATF-Fc,an engineering molecule on tumor growth and metastasis.METHODS：ATF-Fc,an antibody-like molecule comprising the amino-terminal fragment of human uPA （ATF） linked to the Fc fragment of human IgG1 via a flexible linker was developed.Its antitumor activities were evaluated in vitro and in vivo.RESULTS：The results showed that ATF-Fc had obvious cytotoxic effects on several types of tumor cells,which was dependent on the expression of uPAR and the Fc fragment.Treatment with ATF-Fc caused a significant reduction in tumor volume and weight in athymic nude mice s.c.implanted with human MCF-7 breast cancer cells or BGC-823 gastral cancer cells.The inhibition rate of ATF-Fc on MCF-7 and BGC-823-bearing nude mice were 84% and 74%,respectively.The number of liver metastasis and the number of metastatic foci were significantly reduced in mice treated with ATF-Fc,P〈0.001.CONCLUSION：ATF-Fc is a novel therapeutic antibody in the management of solid tumors by disrupting the uPA/uPAR interaction.
出处
《中华肿瘤防治杂志》
CAS
2010年第8期574-578,共5页
Chinese Journal of Cancer Prevention and Treatment
基金
国家自然科学基金(30973670
30970592)
关键词
基因疗法
抗体/治疗应用
肿瘤转移
动物
实验
gene therapy
antibodies/therapeutic usea
neoplasms metastasis
animals
laboratory
