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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 engineered antibody ATF-Fc on tumor growth and metastasis. Methods: Antibody-like molecule ATF-Fc was constructed by linking the amino-terminal fragment of human urokinase (ATF) with the Fc fragment of human IgG1. The antitumor activity of ATF-Fc was evaluated by tumor cells and nude mice bearing tumor model. Results: ATF-Fc had a significant killing effect on many tumor cell lines. The killing effect of ATF-Fc was closely related to the expression of uPAR and the secretion of uPA in tumor cells. ATF-Fc significantly inhibited the growth and tumor liver metastasis of human MCF-7 breast cancer and BGC-823 gastric cancer subcutaneously in nude mice, and its inhibitory rates on MCF-7 and BGC-823 tumors were 84% and 74% %, Compared with the control group, the difference was statistically significant, P <0.001. Conclusion: ATF-Fc is a new anti-tumor antibody whose anti-tumor effect is mediated by interference with uPA / uPAR interaction.