title: A new anti-idiotype antibody capable of binding rituximab on the surface of lymphoma cells.
abstract: The chimeric anti-CD20 monoclonal antibody (mAb), rituximab, is an established part of the management of many non-Hodgkin lymphomas. The in vivo action of rituximab remains elusive, and this partially reflects a lack of highly specific reagents to detect rituximab binding at the cell surface. Here we report a new high-affinity mAb (MB2A4) with fine specificity for the idiotype of rituximab. It is able to detect rituximab in vitro, in the presence of high levels of human immunoglobulin G (IgG), in the serum of patients receiving rituximab therapy, and, surprisingly, when rituximab is bound to CD20 on the cell surface. We propose that the anti-idiotype (Id) binds to rituximab molecules bound univalently at the cell surface, facilitated by the relatively high off-rate of rituximab. This reagent provides new insights into the binding of rituximab at the cell surface and demonstrates a mode of binding that could be exploited for the surface detection of other mAbs with clinical and biologic applications.
authors.affiliation: Tenovus Research Laboratory, Cancer Sciences Division, School of Medicine, University General Hospital, Tremona Road, Southampton, SO16 6YD United Kingdom. msc@soton.ac.uk
authors.forename: Mark S
authors.initials: MS
authors.lastname: Cragg
authors.forename: Mike B
authors.initials: MB
authors.lastname: Bayne
authors.forename: Alison L
authors.initials: AL
authors.lastname: Tutt
authors.forename: Ruth R
authors.initials: RR
authors.lastname: French
authors.forename: Stephen
authors.initials: S
authors.lastname: Beers
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Glennie
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Illidge
mesh_terms: D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000097:blood / Q000276:immunology* / Q000378:metabolism / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20 / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D006801:Humans; D007167:Immunotherapy; D016393:Lymphoma, B-Cell / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology*; D051381:Rats; D000069283:Rituximab
chemical_list: D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D000069283:Rituximab