Antibodies are very efficient drugs, about 70 of them are already approved for medical use, over 500 are in clinical development, and many more are in preclinical development. One important step in the characterization and protection of a therapeutic antibody is the determination of its cognate epitope. The gold standard is the 3D structure of the antibody-antigen complex by crystallography or NMR. However, it remains a tedious task and its outcome is uncertain. We have developed MAbTope, a docking-based prediction method of the epitope associated with straightforward experimental validation procedures. We show that MAbTope predicts the correct epitope for each of 129 tested examples of antibody-antigen complexes of known structure. We further validated this method through the successful determination, and experimental validation (using human embryonic kidney cells 293), of the epitopes recognized by two therapeutic antibodies targeting tumor necrosis factor α (TNF-α): certolizumab and golimumab.
Reference: MAbTope: A Method for Improved Epitope Mapping. Thomas Bourquard, Astrid Musnier, Vincent Puard, Shifa Tahir, Mohammed Akli Ayoub, Yann Jullian, Thomas Boulo, Nathalie Gallay, Hervé Watier, Gilles Bruneau, Eric Reiter, Pascale Crépieux and Anne Poupon. J Immunol, 2018, 201 (10) 3096-3105.