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.

• Authors: M Jules Mattes, Robert M Sharkey, Habibe Karacay, Myron S Czuczman, David M Goldenberg
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 14 Issue 19 Pg. 6154-60 (Oct 01 2008) ISSN: 1078-0432 [Print] United States
• PMID: 18829494 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Antigens, CD20
• Immunoglobulin G
• Sialic Acid Binding Ig-like Lectin 2
• Yttrium Radioisotopes
• epratuzumab

Topics

• Animals
• Antibodies, Monoclonal (chemistry, pharmacology)
• Antibodies, Monoclonal, Humanized
• Antigens, CD20 (chemistry)
• Cell Line, Tumor
• Disease Models, Animal
• Humans
• Immunoglobulin G (chemistry)
• Lymphoma, B-Cell (immunology, metabolism, therapy)
• Male
• Maximum Tolerated Dose
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Neoplasm Transplantation
• Sialic Acid Binding Ig-like Lectin 2 (chemistry)
• Yttrium Radioisotopes (pharmacology)