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IGF-1R anti-idiotypic antibody antagonist exhibited anti-ovarian cancer bioactivity and reduced cisplatin resistance

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Abstract

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.

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Abbreviations

IGF-1R:

Insulin-like growth factor 1R

IGF-1:

Insulin-like growth factor 1

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Acknowledgements

Young and middle-aged health technology innovation leading talent training program of Henan province (YXKC2020012).

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Authors and Affiliations

  1. Department of Gynecology, The First Affiliated Hospital of Zhengzhou University, 1st Jianshe East Road, Zhengzhou, China

    Zhang Weiwei, Xie Ya, Wang Wenwen, Jia Jia, Bai Jing, Zhang Ruitao, Wang Chunfang & Guo Ruixia

  2. Laboratory of Gynecological Malignant Tumor Prevention and Treatment of Henan Province, Zhengzhou, China

    Zhang Weiwei, Wang Chunfang & Guo Ruixia

Authors
  1. Zhang Weiwei
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  2. Xie Ya
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  3. Wang Wenwen
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  4. Jia Jia
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  5. Bai Jing
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  6. Zhang Ruitao
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  7. Wang Chunfang
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  8. Guo Ruixia
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Contributions

ZW, XY, and WW performed the experiments; JJ and BJ drafted the manuscript. ZW and ZR edited the manuscript. WC and GR conceived of the study and participated in its design and coordination.

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Correspondence to Guo Ruixia.

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The authors declare that they have no conflict of interest.

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All animal care and experimental procedures were approved by the first affiliated hospital of Zhengzhou University (2021-KY-0018-001).

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Weiwei, Z., Ya, X., Wenwen, W. et al. IGF-1R anti-idiotypic antibody antagonist exhibited anti-ovarian cancer bioactivity and reduced cisplatin resistance. Human Cell 34, 1197–1214 (2021). https://doi.org/10.1007/s13577-021-00535-x

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  • DOI: https://doi.org/10.1007/s13577-021-00535-x

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