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 Mattes, M. J. Articles by Goldenberg, D. M. Search for Related Content PubMed PubMed Citation Articles by Mattes, M. J. Articles by Goldenberg, D. M.

Therapy of Advanced B-Lymphoma Xenografts with a Combination of ⁹⁰Y-anti-CD22 IgG (Epratuzumab) and Unlabeled Anti-CD20 IgG (Veltuzumab)

Authors' Affiliations: ¹ Garden State Cancer Center, Center for Molecular Medicine and Immunology, Belleville, New Jersey and ² Roswell Park Cancer Institute, Buffalo, New York

Requests for reprints: David M. Goldenberg, Center for Molecular Medicine and Immunology, 520 Belleville Avenue, Belleville, NJ 07109. Phone: 973-844-7000; Fax: 973-844-7020; E-mail: dmg.gscancer{at}att.net.

Purpose: Antibodies are effective therapeutic agents in cancer, but cures are rarely if ever obtained. Combination therapies are likely to be more effective than a single agent. In this study, the combination of a new unconjugated humanized anti-CD20 IgG, veltuzumab, with a ⁹⁰Y-conjugated humanized antibody to CD22 (epratuzumab) was evaluated for the treatment of B-cell lymphoma in a nude mouse model system.

Experimental Design: Nude mice were grafted with the Ramos human B-lymphoma and treatment initiated when tumors were >0.1 cm³. In most experiments, mice were injected first with unconjugated anti-CD20, then with ⁹⁰Y-anti-CD22 1 day later. Additional weekly injections of the unconjugated veltuzumab were administered for 3 weeks. Controls included a single agent only and a nonreactive control radiolabeled antibody.

Results: Unconjugated anti-CD20 veltuzumab alone did not have a significant therapeutic effect, even at a total dose of 2.5 mg per mouse. The ⁹⁰Y-anti-CD22 epratuzumab alone induced marked regressions of all tumors, but they regrew in a few weeks. The combination of these agents cured 80% of the mice. A nonreactive control antibody labeled with ⁹⁰Y, used without veltuzumab, had no therapeutic effect. The therapeutic effect of ⁹⁰Y-epratuzumab required the maximum tolerated dose of radioactivity, which was 160 µCi per mouse.

Conclusions: These studies illustrate how combinations of unconjugated and radioconjugated antibodies against different B-cell markers can improve therapeutic outcome, and offer a new therapeutic paradigm for the treatment of B-cell lymphomas.

This article has been cited by other articles:

				R. M. Sharkey, O. W. Press, and D. M. Goldenberg A re-examination of radioimmunotherapy in the treatment of non-Hodgkin lymphoma: prospects for dual-targeted antibody/radioantibody therapy Blood, April 23, 2009; 113(17): 3891 - 3895. [Abstract] [Full Text] [PDF]

				R. M. Sharkey, H. Karacay, C. R. Johnson, S. Litwin, E. A. Rossi, W. J. McBride, C.-H. Chang, and D. M. Goldenberg Pretargeted Versus Directly Targeted Radioimmunotherapy Combined with Anti-CD20 Antibody Consolidation Therapy of Non-Hodgkin Lymphoma J. Nucl. Med., March 1, 2009; 50(3): 444 - 453. [Abstract] [Full Text] [PDF]