Epitope interactions of monoclonal antibodies targeting CD20 and their relationship to functional properties

 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.

Full Text Options
Article
Metrics
 Share
 Full Text
 Info
Pages
22 - 33
doi
10.4161/mabs.22771
Type
Review
 Metrics
 Cite This Article
 Permissions
Creative Commons License Permissions
 Reprints
Epitope interactions of monoclonal antibodies targeting CD20 and their relationship to functional properties