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RETRACTED ARTICLE: Structure-based development and optimization of therapy antibody drugs against TNFα

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This article was retracted on 09 December 2015

Abstract

Previously, we reported on the crystal structures of the Fab fragments of two food and drug administration approved therapeutic antibodies, Infliximab and Adalimumab, in complex with TNFα. The structurally identified epitopes on TNFα reveal the mechanism of TNFα inhibition by partially overlapping with the TNFα-receptor interface. In this study, we launched a screen of a phage display library to isolate novel anti-TNFα antibodies based on the adalimumab epitope. Structural analysis, the phage display antibody isolation technology, step-by-step antibody optimization, complementarity-determining region residues random mutagenesis, phage ELISA, binding affinity characterization, and cell signaling assays were used for the development and optimization of the novel anti-TNFα antibodies. Moreover, one of the novel antibodies, hAta09, has a superior inhibitory effect on TNFα function and signaling. Taken together, our report established that the novel anti-TNFα antibody hAta09 may achieve clinical efficacy in a TNFα-associated disease.

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Acknowledgments

We thank Celplor LLC and ProMab Biotechnologies, Inc., for help on mammalian cell based recombinant protein production; Dr. Cheng Chen, of Tianjin University, and Dr. Tai An, of Union Medical College, for helpful discussions. This work was supported by the National Natural Science Foundation of China (Grant nos. 31170678 and 31000332).

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Author notes

    Authors and Affiliations

    1. Key Laboratory of Oncology, Cancer Center, Chinese PLA General Hospital and Chinese PLA Medical School, Beijing, People’s Republic of China

      Wenyan Fu, Shi Hu, Jian Zhao & Yajun Guo

    2. Translational Medicine Research Institute and International Joint Cancer Institute, The Second Military Medical University, Shanghai, People’s Republic of China

      Wenyan Fu, Shi Hu, Jian Zhao & Yajun Guo

    3. Tianjin Joint Academy of Biomedicine and Technology, Tianjin, 300457, People’s Republic of China

      Wenyan Fu, Hiroaki Takeda & Augus N. Bethune

    4. Graduate School of Medicine, Nagoya University, Showa-ku, Nagoya, Japan

      Xiaoze Wang

    5. School of Medicine, Nankai University, Tianjin, People’s Republic of China

      Xiaoze Wang, Weili Yang & Yajun Guo

    6. Department of Biomedicine, Nagoya University, Showa-ku, Nagoya, Japan

      Hiroaki Takeda

    7. Laboratory of Structural Biology and MOE Laboratory of Protein Science, School of Medicine, Tsinghua University, Beijing, People’s Republic of China

      Zhiyong Lou

    8. Molecular Drug Discovery Center, Xi’an Jinwa Pharmaceutical Co., Ltd, Xi’an, 710000, Shaanxi, People’s Republic of China

      Augus N. Bethune

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    1. Wenyan Fu
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    Corresponding authors

    Correspondence to Augus N. Bethune or Yajun Guo.

    Additional information

    Handling Editor: D. Tsikas.

    Wenyan Fu, Xiaoze Wang, and Weili Yang have contributed equally to this study.

    The Publisher and Editor retract this article in accordance with the recommendations of the Committee on Publication Ethics (COPE). After a thorough investigation we have strong reason to believe that the peer review process was compromised. In addition some author identities and given institutional addresses could not be confirmed.

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    Fu, W., Wang, X., Yang, W. et al. RETRACTED ARTICLE: Structure-based development and optimization of therapy antibody drugs against TNFα. Amino Acids 47, 1259–1266 (2015). https://doi.org/10.1007/s00726-015-1954-9

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    • DOI: https://doi.org/10.1007/s00726-015-1954-9

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