Antibody Engineering Toward Enhancement of Teplizumab Anti-CD3 Binding Affinity in Type 1 Diabetes Prevention and Treatment

Fateme  Sefid; Kimia  Monshizadeh; Roya  Ghenaatzadeh; Zahra  Roodgarpour; Ghasem  Azamirad; Hamid  Mirhosseini

doi:10.18502/ijdo.v17i2.18848

Fateme Sefid Department of Medical Genetics, Shahid Sadoughi University of Medical Science, Yazd, Iran.
Kimia Monshizadeh Department of Medical Genetics, Shahid Sadoughi University of Medical Science, Yazd, Iran.
Roya Ghenaatzadeh Research Center for Health Technology Assessment and Medical Informatics, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
Zahra Roodgarpour Research Center for Health Technology Assessment and Medical Informatics, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
Ghasem Azamirad Department of Mechanical Engineering, Yazd University, Yazd, Iran.
Hamid Mirhosseini Research Center for Health Technology Assessment and Medical Informatics, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

DOI: https://doi.org/10.18502/ijdo.v17i2.18848

Keywords: Teplizumab, Antibody Engineering, Type 1 diabetes

Abstract

Objective: The monoclonal antibodies with CD3 target have the potential to change the progression of type 1 diabetes (T1D) and enhance the longevity of beta-cell function. The main objective of the study is antibody engineering toward Enhancement of Teplizumab Anti-CD3 Binding Affinity in T1D prevention and treatment.

Materials and Methods: We aimed at finding the important amino acids of this antibody, and then replaced these amino acids with others to improve their binding affinity, and examine the binding affinity of antibody variants to antigens. In the end, we selected high-affinity variants of the antibody according to results of High Ambiguity Driven biomolecular DOCKing (HADDOCK).

Results: Our research indicated that 14 mutated variants were able to enhance the binding characteristics of Ab in comparison to standard antibodies.

Conclusion: The altered antibodies could serve as promising options for enhanced affinity binding to antigens, which could affect the specificity and sensitivity of antibodies.