title: Rituximab blocks binding of radiolabeled anti-CD20 antibodies (Ab) but not radiolabeled anti-CD45 Ab.
abstract: Rituximab therapy is associated with a long in vivo persistence, yet little is known about the effect of circulating rituximab on B-cell non-Hodgkin lymphoma (B-NHL) targeting by the other available anti-CD20 monoclonal antibodies (MoAbs) (131)iodine-tositumomab and (90)yttrium-ibritumomab tiuxetan. Therefore we assessed the impact of preexisting rituximab on the binding and efficacy of second anti-CD20 MoAbs to B-NHL and determined whether targeting an alternative lymphoma-associated antigen, CD45, could circumvent this effect. We demonstrated that rituximab concentrations as low as 5 microg/mL nearly completely blocked the binding of a second anti-CD20 MoAbs (P < .001), but had no impact on CD45 targeting (P = .89). Serum from patients with distant exposures to rituximab also blocked binding of anti-CD20 MoAbs to patient-derived rituximab-naive B-NHL at concentrations at low as 7 microg/mL, but did not affect CD45 ligation. A mouse xenograft model (Granta, FL-18, Ramos cell lines) showed that rituximab pretreatment significantly reduced B-NHL targeting and tumor control by CD20-directed radioimmunotherapy (RIT), but had no impact on targeting CD45. These findings suggest that circulating rituximab impairs the clinical efficacy of CD20-directed RIT, imply that novel anti-CD20 MoAbs could also face this same limitation, and indicate that CD45 may represent an alternative target for RIT in B-NHL.
authors.affiliation: Department of Medicine, Division of Medical Oncology, University of Washington, Fred Hutchinson Cancer Research Center, Seattle, WA 98195, USA. agopal@u.washington.edu
authors.forename: Ajay K
authors.initials: AK
authors.lastname: Gopal
authors.forename: Oliver W
authors.initials: OW
authors.lastname: Press
authors.forename: Shani M
authors.initials: SM
authors.lastname: Wilbur
authors.forename: David G
authors.initials: DG
authors.lastname: Maloney
authors.forename: John M
authors.initials: JM
authors.lastname: Pagel
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20 / Q000276:immunology*; D000971:Antineoplastic Combined Chemotherapy Protocols; D004347:Drug Interactions; D005260:Female; D006801:Humans; D018796:Immunoconjugates / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D007457:Iodine Radioisotopes; D017493:Leukocyte Common Antigens / Q000276:immunology*; D016393:Lymphoma, B-Cell / Q000628:therapy*; D051379:Mice; D008819:Mice, Nude; D016499:Radioimmunotherapy / Q000379:methods*; D000069283:Rituximab; D023041:Xenograft Model Antitumor Assays; D015021:Yttrium Radioisotopes
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D018796:Immunoconjugates; D007457:Iodine Radioisotopes; D015021:Yttrium Radioisotopes; D000069283:Rituximab; D017493:Leukocyte Common Antigens