This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Vallera, D. A. Articles by Vitetta, E. S. Search for Related Content PubMed PubMed Citation Articles by Vallera, D. A. Articles by Vitetta, E. S.

Radioimmunotherapy of CD22-Expressing Daudi Tumors in Nude Mice with a ⁹⁰Y-Labeled Anti-CD22 Monoclonal Antibody

Authors' Affiliations: Departments of ¹ Therapeutic Radiology-Radiation Oncology, ² Medicine, ³ Pediatrics, and ⁴ Orthopedic Surgery, University of Minnesota Cancer Center, Minneapolis, Minnesota; ⁵ Radioimmune and Inorganic Chemistry Section, Radiation Oncology Branch, National Cancer Institute, Bethesda, Maryland; and ⁶ Cancer Immunobiology Center, University of Texas, Southwestern Medical School, Dallas, Texas

Requests for reprints: Daniel A. Vallera, Department of Therapeutic Radiology-Radiation Oncology, University of Minnesota Cancer Center, MMC 367, Minneapolis, MN 55455. Phone: 612-626-6664; Fax: 612-624-3913; E-mail: valle001{at}umn.edu.

A study was undertaken to investigate the efficacy of a high affinity, rapidly internalizing anti-CD22 monoclonal antibody for selectively delivering high-energy ⁹⁰Y radioactivity to B lymphoma cells in vivo. The antibody, RFB4, was readily labeled with ⁹⁰Y 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 ⁹⁰Y-labeled anti-CD22 (Y22) was dose-dependent, irreversible, and the best results were achieved in mice receiving a single i.p. dose of 196 µCi. 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.

This article has been cited by other articles:

				M. J. Mattes, R. M. Sharkey, H. Karacay, M. S. Czuczman, and D. M. Goldenberg Therapy of Advanced B-Lymphoma Xenografts with a Combination of 90Y-anti-CD22 IgG (Epratuzumab) and Unlabeled Anti-CD20 IgG (Veltuzumab) Clin. Cancer Res., October 1, 2008; 14(19): 6154 - 6160. [Abstract] [Full Text] [PDF]