title: Radioimmunotherapy of CD22-expressing Daudi tumors in nude mice with a 90Y-labeled anti-CD22 monoclonal antibody.
abstract: A study was undertaken to investigate the efficacy of a high affinity, rapidly internalizing anti-CD22 monoclonal antibody for selectively delivering high-energy (90)Y radioactivity to B lymphoma cells in vivo. The antibody, RFB4, was readily labeled with (90)Y using the highly stable chelate, 1B4M-diethylenetriaminepentaacetic acid. Labeled RFB4 selectively bound to the CD22(+) Burkitt's lymphoma cell line Daudi, but not to CD22(-) control cells in vitro as compared with a control antibody, and was more significantly bound (P = 0.03) to Daudi solid tumors growing in athymic nude mice. Biodistribution data correlated well with the antitumor effect. The therapeutic effect of (90)Y-labeled anti-CD22 (Y22) was dose-dependent, irreversible, and the best results were achieved in mice receiving a single i.p. dose of 196 microCi. These mice displayed a significantly better (P < 0.01) antitumor response than control mice and survived >200 days with no evidence of tumor. Histology studies showed no significant injury to kidney, liver, or small intestine. Importantly, tumor-bearing mice treated with Y22 had no radiologic bone marrow damage compared with tumor-bearing mice treated with the control-labeled antibody arguing that the presence of CD22(+) tumor protected mice from bone marrow damage. When anti-CD22 radioimmunotherapy was compared to radioimmunotherapy with anti-CD19 and anti-CD45 antibodies, all three antibodies distributed significantly high levels of radioisotope to flank tumors in vivo compared with controls (P < 0.05), induced complete remission, and produced long-term, tumor-free survivors. These findings indicate that anti-CD22 radioimmunotherapy with Y22 is highly effective in vivo against CD22-expressing malignancies and may be a useful therapy for drug-refractory B cell leukemia patients.
authors.affiliation: Department of Therapeutic Radiology-Radiation Oncology, University of Minnesota Cancer Center, Minneapolis, 55455, USA. valle001@umn.edu
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Vallera
authors.forename: Martin W
authors.initials: MW
authors.lastname: Brechbiel
authors.forename: Linda J
authors.initials: LJ
authors.lastname: Burns
authors.forename: Angela
authors.initials: A
authors.lastname: Panoskaltsis-Mortari
authors.forename: Katie E
authors.initials: KE
authors.lastname: Dusenbery
authors.forename: Dennis R
authors.initials: DR
authors.lastname: Clohisy
authors.forename: Ellen S
authors.initials: ES
authors.lastname: Vitetta
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry*; D018941:Antigens, CD19 / Q000096:biosynthesis; D000944:Antigens, Differentiation, B-Lymphocyte / Q000737:chemistry; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology; D001854:Bone Marrow Cells / Q000166:cytology; D045744:Cell Line, Tumor; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D006825:Hybridomas / Q000473:pathology; D017493:Leukocyte Common Antigens / Q000096:biosynthesis; D051379:Mice; D008819:Mice, Nude; D011485:Protein Binding; D016499:Radioimmunotherapy / Q000379:methods*; D051918:Sialic Acid Binding Ig-like Lectin 2 / Q000096:biosynthesis*; D013997:Time Factors; D014018:Tissue Distribution; D015021:Yttrium Radioisotopes
chemical_list: D000911:Antibodies, Monoclonal; D018941:Antigens, CD19; D000944:Antigens, Differentiation, B-Lymphocyte; D051918:Sialic Acid Binding Ig-like Lectin 2; D015021:Yttrium Radioisotopes; D017493:Leukocyte Common Antigens