1. Epitope interactions of monoclonal antibodies targeting CD20 and their relationship to functional properties
- Author
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Guy Georges, Pablo Umana, Manfred Schwaiger, Ekkehard Mössner, Christian Klein, Alfred Lammens, Gerhard Niederfellner, Karl-Peter Hopfner, and Wolfgang Schäfer
- Subjects
Linear epitope ,biology ,medicine.drug_class ,Immunology ,Review ,Monoclonal antibody ,Fragment crystallizable region ,Primary and secondary antibodies ,Virology ,Molecular biology ,Epitope ,Epitope mapping ,Antigen ,immune system diseases ,hemic and lymphatic diseases ,medicine ,biology.protein ,Immunology and Allergy ,Antibody - Abstract
Several novel anti-CD20 monoclonal antibodies are currently in development with the aim of improving the treatment of B cell malignancies. Mutagenesis and epitope mapping studies have revealed differences between the CD20 epitopes recognized by these antibodies. Recently, X-ray crystallography studies confirmed that the Type I CD20 antibody rituximab and the Type II CD20 antibody obinutuzumab (GA101) differ fundamentally in their interaction with CD20 despite recognizing a partially overlapping epitope on CD20. The Type I CD20 antibodies rituximab and ofatumumab are known to bind to different epitopes. The differences suggest that the biological properties of these antibodies are not solely determined by their core epitope sequences, but also depend on other factors, such as the elbow hinge angle, the orientation of the bound antibody and differential effects mediated by the Fc region of the antibody. Taken together, these factors may explain differences in the preclinical properties and clinical efficacy of anti-CD20 antibodies.
- Published
- 2013