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


METHODS
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.
Mattes
M Jules
MJ
Garden State Cancer Center, Center for Molecular Medicine and Immunology, 520 Belleville Avenue, Belleville, NJ 07109, USA.
Sharkey
Robert M
RM
Karacay
Habibe
H
Czuczman
Myron S
MS
Goldenberg
David M
DM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D018951:Antigens, CD20 / Q000737:chemistry*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry*; D016393:Lymphoma, B-Cell / Q000276:immunology / Q000378:metabolism* / Q000628:therapy*; D008297:Male; D020714:Maximum Tolerated Dose; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D051918:Sialic Acid Binding Ig-like Lectin 2 / Q000737:chemistry*; D015021:Yttrium Radioisotopes / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018951:Antigens, CD20; D007074:Immunoglobulin G; D051918:Sialic Acid Binding Ig-like Lectin 2; D015021:Yttrium Radioisotopes; C448700:epratuzumab