抗ErbB2 ScFv-Fc-IL-2融合蛋白在体外和体内对过表达ErbB2的肿瘤细胞具有高效的生长抑制作用。
Efficient growth inhibition of ErbB2-overexpressing tumor cells by anti-ErbB2 ScFv-Fc-IL-2 fusion protein in vitro and in vivo.
作者信息
Shi Ming, Zhang Ling, Gu Hong-Tao, Jiang Feng-Qin, Qian Lu, Yu Ming, Chen Guo-Jiang, Luo Qun, Shen Bei-Fen, Guo Ning
机构信息
Institute of Basic Medical Sciences, Beijing 100850, China.
出版信息
Acta Pharmacol Sin. 2007 Oct;28(10):1611-20. doi: 10.1111/j.1745-7254.2007.00622.x.
AIM
To investigate the antitumor activities of an anti-ErbB2 scFv-Fc-interleukin 2 (IL-2) fusion protein (HFI) in vitro and in vivo.
METHODS
Fusion protein HFI was constructed. The efficacy of HFI in mediating tumor cell lysis was determined by colorimetric lactate dehydrogenase release assays. The antitumor activity of HFI was evaluated in tumor xenograft models.
RESULTS
The fusion protein was folded as a homodimer formed by covalently linking Fc portions and it retained ErbB2 specificity and IL-2 biological activity. HFI mediated antibody-dependent cell-mediated cytotoxicity (ADCC) at low effector-to-target ratios in vitro and improved the therapeutic efficacy of IL-2 in experiments in vivo.
CONCLUSION
The genetically-engineered anti-ErbB2 scFv-Fc-IL-2 fusion protein exhibited high efficiency both in mediating ADCC in vitro and significant antitumor activity in tumor xenograft models.
目的
研究抗ErbB2单链抗体片段-免疫球蛋白Fc段-白细胞介素2（IL-2）融合蛋白（HFI）的体内外抗肿瘤活性。
方法
构建融合蛋白HFI。通过比色法乳酸脱氢酶释放试验测定HFI介导肿瘤细胞裂解的效力。在肿瘤异种移植模型中评估HFI的抗肿瘤活性。
结果
该融合蛋白折叠成由Fc部分共价连接形成的同源二聚体，保留了ErbB2特异性和IL-2生物学活性。HFI在体外低效应细胞与靶细胞比例下介导抗体依赖性细胞介导的细胞毒性（ADCC），并在体内实验中提高了IL-2的治疗效果。
结论
基因工程抗ErbB2单链抗体片段-Fc-IL-2融合蛋白在体外介导ADCC以及在肿瘤异种移植模型中均表现出高效的显著抗肿瘤活性。
Zotero 插件