title: Evaluation of CD20, CD22, and HLA-DR targeting for radioimmunotherapy of B-cell lymphomas.
abstract: Despite the promise of radioimmunotherapy using anti-CD20 antibodies (Ab) for the treatment of relapsed patients with indolent non-Hodgkin lymphoma (NHL), most patients treated with conventional doses of (131)I-tositumomab or (90)Y-ibritumomab eventually relapse. We did comparative assessments using conventional radioimmunotherapy targeting CD20, CD22, and HLA-DR on human Ramos, Raji, and FL-18 lymphoma xenografts in athymic mice to assess the potential for improving the efficacy of radioimmunotherapy by targeting other NHL cell surface antigens. Results of biodistribution studies showed significant differences in tumor localization consistent with variable antigenic expression on the different lymphoma cell lines. Interestingly, the radioimmunoconjugate that yielded the best tumor-to-normal organ ratios differed in each tumor model. We also explored administering all three (111)In-1,4,7,10-tetra-azacylododecane N,N',N'',N'''-tetraacetic acid antibodies in combination, but discovered, surprisingly, that this approach did not augment the localization of radioactivity to tumors compared with the administration of the best single radiolabeled Ab alone. These data suggest that conventional radioimmunotherapy using anti-CD20, anti-HLA-DR, or anti-CD22 Abs is effective when used singly and provides targeted uptake of radiolabel into the tumor that is dependent on the levels of antigen expression. Improvements in tumor-to-normal organ ratios of radioactivity cannot be achieved using directly labeled Abs in combination but may be afforded by novel pretargeting methods.
authors.affiliation: Fred Hutchinson Cancer Research Center, University of Washington, and Aletheon Pharmaceuticals, Inc., Seattle, Washington 98109, USA. jpagel@fhcrc.org
authors.forename: John M
authors.initials: JM
authors.lastname: Pagel
authors.forename: Anastasia
authors.initials: A
authors.lastname: Pantelias
authors.forename: Nathan
authors.initials: N
authors.lastname: Hedin
authors.forename: Shani
authors.initials: S
authors.lastname: Wilbur
authors.forename: Laura
authors.initials: L
authors.lastname: Saganic
authors.forename: Yukang
authors.initials: Y
authors.lastname: Lin
authors.forename: Donald
authors.initials: D
authors.lastname: Axworthy
authors.forename: Donald K
authors.initials: DK
authors.lastname: Hamlin
authors.forename: D Scott
authors.initials: DS
authors.lastname: Wilbur
authors.forename: Ajay K
authors.initials: AK
authors.lastname: Gopal
authors.forename: Oliver W
authors.initials: OW
authors.lastname: Press
mesh_terms: D000818:Animals; D000906:Antibodies / Q000008:administration & dosage*; D015703:Antigens, CD / Q000276:immunology*; D018951:Antigens, CD20 / Q000276:immunology; D045744:Cell Line, Tumor; D002614:Chelating Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D005434:Flow Cytometry; D006684:HLA-DR Antigens / Q000276:immunology*; D006573:Heterocyclic Compounds, 1-Ring / Q000008:administration & dosage / Q000493:pharmacokinetics; D006801:Humans; D007205:Indium Radioisotopes / Q000008:administration & dosage / Q000493:pharmacokinetics; D016393:Lymphoma, B-Cell / Q000532:radiotherapy*; D051379:Mice; D008819:Mice, Nude; D016499:Radioimmunotherapy / Q000379:methods*; D051918:Sialic Acid Binding Ig-like Lectin 2 / Q000276:immunology; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
chemical_list: D000906:Antibodies; D015703:Antigens, CD; D018951:Antigens, CD20; D002614:Chelating Agents; D006684:HLA-DR Antigens; D006573:Heterocyclic Compounds, 1-Ring; D007205:Indium Radioisotopes; D051918:Sialic Acid Binding Ig-like Lectin 2; C071349:1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid