title: 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.
authors.affiliation: Discovery Oncology, Pharma Research and Early Development, Roche Glycart AG, Schlieren, Switzerland. christian.klein.ck1@roche.com
authors.forename: Christian
authors.initials: C
authors.lastname: Klein
authors.forename: Alfred
authors.initials: A
authors.lastname: Lammens
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Schäfer
authors.forename: Guy
authors.initials: G
authors.lastname: Georges
authors.forename: Manfred
authors.initials: M
authors.lastname: Schwaiger
authors.forename: Ekkehard
authors.initials: E
authors.lastname: Mössner
authors.forename: Karl-Peter
authors.initials: KP
authors.lastname: Hopfner
authors.forename: Pablo
authors.initials: P
authors.lastname: Umaña
authors.forename: Gerhard
authors.initials: G
authors.lastname: Niederfellner
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000276:immunology / Q000378:metabolism / Q000627:therapeutic use; D058846:Antibodies, Monoclonal, Murine-Derived / Q000276:immunology / Q000378:metabolism / Q000627:therapeutic use; D018951:Antigens, CD20 / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D002986:Clinical Trials as Topic; D018360:Crystallography, X-Ray; D018604:Epitope Mapping; D000939:Epitopes / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000628:therapy; D008228:Lymphoma, Non-Hodgkin / Q000628:therapy; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D000069283:Rituximab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D000939:Epitopes; D000069283:Rituximab; C527517:ofatumumab; C543332:obinutuzumab