Chen Chen, Liang Hui, Liao Xinmei, Pan Jian, Chen Jianhe, Zhao Shibi, Xu Yan, Wu Yun, Ni Jian
Translational Research Center, Second Hospital, The Second Clinical School, Nanjing Medical University, Nanjing, China.
Human Antibodomics Suzhou Industrial Park, Suzhou, China.
Tumour Biol. 2016 Dec;37:15903–15912. doi: 10.1007/s13277-016-5423-1. Epub 2016 Oct 4.
Inhibition of tumor vasculature is an effective strategy for cancer therapy. Angiostatin could suppress tumor growth and metastasis by binding and inhibiting F1F0 ATP synthase on the endothelial cell surface. We previously screened a monoclonal antibody (McAb, McAb178-5G10), which specifically bound to ATPase on the surface of cells and showed an angiostatin-like activity. Here, we further generated a panel of CHO-mAb subclone stable expressing a humanized chimeric antibody from hybridoma cell McAb178-5G10 by gene engineer. And then, we successfully expressed the humanized antibody Hai178 at high level in a 5-L wave bioreactor. The vitro results showed that Hai178 retained the specific binding and antitumor activity of murine antibody. Furthermore, Hai178 also had a tumor therapeutic effect in tumor xenografts. These results paved the way for Hai178 as a therapeutic antibody in clinic.
抑制肿瘤血管生成是一种有效的癌症治疗策略。血管抑素可通过结合并抑制内皮细胞表面的F1F0 ATP合酶来抑制肿瘤生长和转移。我们之前筛选出一种单克隆抗体(McAb,McAb178-5G10),它能特异性结合细胞表面的ATP酶并表现出类似血管抑素的活性。在此,我们通过基因工程进一步从杂交瘤细胞McAb178-5G10中生成了一组稳定表达人源化嵌合抗体的CHO-mAb亚克隆。然后,我们在5-L波浪式生物反应器中成功高水平表达了人源化抗体Hai178。体外实验结果表明,Hai178保留了鼠源抗体的特异性结合和抗肿瘤活性。此外,Hai178在肿瘤异种移植模型中也具有肿瘤治疗效果。这些结果为Hai178作为临床治疗性抗体铺平了道路。