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: Daniel A Vallera, Martin W Brechbiel, Linda J Burns, Angela Panoskaltsis-Mortari, Katie E Dusenbery, Dennis R Clohisy, Ellen S Vitetta
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 11 Issue 21 Pg. 7920-8 (Nov 01 2005) ISSN: 1078-0432 [Print] United States
• PMID: 16278417 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antigens, CD19
• Antigens, Differentiation, B-Lymphocyte
• Sialic Acid Binding Ig-like Lectin 2
• Yttrium Radioisotopes
• Leukocyte Common Antigens

Topics

• Animals
• Antibodies, Monoclonal (chemistry)
• Antigens, CD19 (biosynthesis)
• Antigens, Differentiation, B-Lymphocyte (chemistry)
• Bone Marrow (metabolism, pathology)
• Bone Marrow Cells (cytology)
• Cell Line, Tumor
• Female
• Flow Cytometry
• Humans
• Hybridomas (pathology)
• Leukocyte Common Antigens (biosynthesis)
• Mice
• Mice, Nude
• Protein Binding
• Radioimmunotherapy (methods)
• Sialic Acid Binding Ig-like Lectin 2 (biosynthesis)
• Time Factors
• Tissue Distribution
• Yttrium Radioisotopes