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.
Subject(s)
Antibodies, Monoclonal/chemistry , Radioimmunotherapy/methods , Sialic Acid Binding Ig-like Lectin 2/biosynthesis , Yttrium Radioisotopes , Animals , Antigens, CD19/biosynthesis , Antigens, Differentiation, B-Lymphocyte/chemistry , Bone Marrow/metabolism , Bone Marrow/pathology , Bone Marrow Cells/cytology , Cell Line, Tumor , Female , Flow Cytometry , Humans , Hybridomas/pathology , Leukocyte Common Antigens/biosynthesis , Mice , Mice, Nude , Protein Binding , Time Factors , Tissue DistributionABSTRACT
The current introduction summarizes the five scientific sessions (bone marrow microenvironment and animal models of bone metastasis; prostate carcinoma; multiple myeloma; breast carcinoma; and preclinical and clinical studies on metastasis: future directions) and provides an overview of the proceedings of the Third North American Symposium on Skeletal Complications of Malignancy, Bethesda, Maryland, April 25-27, 2002.
