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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.