Ofatumumab Monoclonal Antibody Affinity Maturation Through in silico Modeling

نویسندگان

  • Mortazavi, Yousef Department of Medical Biotechnology and Nanotechnology, Faculty of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
  • Payandeh, Zahra Department of Medical Biotechnology and Nanotechnology, Faculty of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
  • Rahimpour, Azam School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  • Rajabibazl, Masoumeh Department of Clinical Biochemistry, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  • Taromchi, Amir Hossein Department of Medical Biotechnology and Nanotechnology, Faculty of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
چکیده مقاله:

Background: Ofatumumab, an anti-CD20 mAb, was approved in 2009 for the treatment of chronic lymphocytic leukemia. This mAb acts through immune-mediated mechanisms, in particular complement-dependent cytotoxicity and antibody-dependent cellular cytotoxicity by natural killer cells as well as antibody-dependent phagocytosis by macrophages. Apoptosis induction is another mechanism of this antibody. Computational docking is the method of predicting the conformation of an antibody-antigen from its separated elements. Validation of the designed antibodies is carried out by docking tools. Increased affinity enhances the biological action of the antibody, which in turn improves the therapeutic effects. Furthermore, the increased antibody affinity can reduce the therapeutic dose of the antibody, resulting in lower toxicity and handling cost. Methods: Considering the importance of this issue, using in silico analysis such as docking and molecular dynamics, we aimed to find the important amino acids of the Ofatumumab antibody and then replaced these amino acids with others to improve antibody-binding affinity. Finally, we examined the binding affinity of antibody variants to antigen. Results: Our findings showed that variant 3 mutations have improved the characteristics of antibody binding compared to normal Ofatumumab antibodies.  Conclusion: The designed anti-CD20 antibodies showed potentiality for improved affinity in comparison to commercial Ofatumumab. 

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عنوان ژورنال

دوره 22  شماره 3

صفحات  180- 192

تاریخ انتشار 2018-05

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