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IGF-1R anti-idiotypic antibody antagonist exhibited anti-ovarian cancer bioactivity and reduced cisplatin resistance
Human Cell ( IF 3.4 ) Pub Date : 2021-04-27 , DOI: 10.1007/s13577-021-00535-x
Zhang Weiwei 1, 2 , Xie Ya 1 , Wang Wenwen 1 , Jia Jia 1 , Bai Jing 1 , Zhang Ruitao 1 , Wang Chunfang 1, 2 , Guo Ruixia 1, 2
Affiliation  

Ovarian cancer is the most deadly gynecological malignant tumor in the world today. Previous studies have shown that insulin-like growth factor-1 receptor (IGF-1R) is closely related to the occurrence and development of ovarian cancer, and ovarian cancer cells endogenously express high IGF-1R. Therefore, IGF-1R could be used as a target for ovarian cancer treatment. In the past, the strategy for preparing IGF-1R antagonists was to use IGF-1R antibody and small-molecule inhibitor. In the current research, we use a new method to prepare IGF-1R antagonists. We prepared a series of IGF-1 internal imaging anti-idiotypic antibodies by anti-idiotypic antibody strategy. After a series of screening and identification, one of the anti-idiotypic antibodies (B003-2A) was selected for further evaluation, and the results showed that B003-2A could not only inhibit the binding of IGF-1 to IGF-1R but also inhibit the signaling mediated by IGF-1R. Further work showed that B003-2A inhibited the proliferation of ovarian cancer cells in vivo and in vitro. In addition, the current study also indicates that B003-2A could enhance the sensitivity of cisplatin in cisplatin-resistant ovarian cancer cell lines. In summary, our research shows that B003-2A can be used to treat ovarian cancer. The current study also laid the foundation for the development of IGF-1R antagonist.



中文翻译:


IGF-1R 抗独特型抗体拮抗剂表现出抗卵巢癌生物活性并降低顺铂耐药性



卵巢癌是当今世界上最致命的妇科恶性肿瘤。前期研究表明胰岛素样生长因子1受体(IGF-1R)与卵巢癌的发生发展密切相关,卵巢癌细胞内源性高表达IGF-1R。因此,IGF-1R可作为卵巢癌治疗的靶点。过去制备IGF-1R拮抗剂的策略是使用IGF-1R抗体和小分子抑制剂。在目前的研究中,我们采用了一种新方法来制备IGF-1R拮抗剂。我们通过抗独特型抗体策略制备了一系列IGF-1内部显像抗独特型抗体。经过一系列的筛选和鉴定,选择其中一种抗独特型抗体(B003-2A)进行进一步评价,结果表明B003-2A不仅能抑制IGF-1与IGF-1R的结合,还能抑制IGF-1与IGF-1R的结合。抑制 IGF-1R 介导的信号传导。进一步的工作表明B003-2A在体内和体外均抑制卵巢癌细胞的增殖。此外,目前的研究还表明,B003-2A可以增强顺铂耐药的卵巢癌细胞系对顺铂的敏感性。总之,我们的研究表明B003-2A可用于治疗卵巢癌。目前的研究也为IGF-1R拮抗剂的开发奠定了基础。

更新日期:2021-06-13
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