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Development and Optimization of Therapeutic Analogues of Anti-TNFα Antibody Infliximab
Ist Teil von
Molecular biology (New York), 2018-07, Vol.52 (4), p.543-547
Ort / Verlag
Moscow: Pleiades Publishing
Erscheinungsjahr
2018
Quelle
SpringerLink
Beschreibungen/Notizen
Previously, we have reported the crystal structures of Fab fragment of Infliximab in complex with TNFα. The structurally identified epitope on TNFα revealed the mechanism of TNFα inhibition by partially overlapping with the TNFα-receptor interface and the possibility to optimize the binding affinity. In this study, we launched a screen of a phage display library to isolate novel anti-TNFα antibodies based on the infliximab epitope. To develop novel anti-TNFα antibodies, structural analysis, the phage display antibody isolation, step by step antibody optimization, CDR residues random mutagenesis, and binding affinity characterization were performed. One of the novel antibodies generated on the backbone of infliximab, Inf3D6, has the superior binding affinity to
TNFα
, thus, demonstrating the potential for structure guided optimization for improvement of existing antibody-based therapeutics.