Therapy of advanced B-lymphoma xenografts with a combination of 90Y-anti-CD22 IgG (epratuzumab) and unlabeled anti-CD20 IgG (veltuzumab).

ABSTRACT

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 (90)Y-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 cm(3). In most experiments, mice were injected first with unconjugated anti-CD20, then with (90)Y-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 (90)Y-anti-CD22 epratuzumab alone induced marked regressions of all tumors, but they regrew in a few weeks. The combination of these agents cured approximately 80% of the mice. A nonreactive control antibody labeled with (90)Y, used without veltuzumab, had no therapeutic effect. The therapeutic effect of (90)Y-epratuzumab required the maximum tolerated dose of radioactivity, which was 160 muCi 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.