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Therapy of B-lymphoma xenografts with a combination of unconjugated anti-CD20 and 90-Y-anti-CD22 antibodies

¹ Ctr for Molecular Medicine and Immunology, Belleville, New Jersey

432

Objectives: Unconjugated and radioconjugated anti-CD20 antibodies have been used successfully in treating non-Hodgkin’s lymphoma. Other radioconjugates, such as radiolabeled anti-CD22 IgG, have also been effective clinically, and because a different antigen is targeted, this treatment might benefit from a combination with an unconjugated anti-CD20 IgG. We have examined this possibility.

Methods: Nude mice bearing established s.c. Ramos human B-cell lymphoma xenografts (>0.1 cm3) were given the maximum tolerated dose of 90Y-anti-CD22 (epratuzumab, Immunomedics, Inc.) (0.160 mCi = 5.9 MBq) alone or pre-dosed one day earlier with the unconjugated anti-CD20 IgG (veltuzumab, Immunomedics, Inc.), and then followed with 3 additional weekly injections of the unconjugated IgG.

Results: Tumors responded initially to the 90Y-epratuzumab alone, but after a few weeks regrew. Unconjugated anti-CD20 IgG given over 4 weeks at a total dose of 2.5 mg had no significant anti-tumor effect. However, approximately 85% of tumors in animals given the combination of a single dose of 90Y-epratuzumab with the 4 weekly injections of anti-CD20 regressed completely with no evidence of regrowth over a period of 5 months. This combination effect was observed with a little as 0.25 mg total dose of the anti-CD20. The effect of the radioconjugated Ab was antigen-specific, since a non-reactive Ab labeled in the same way had no therapeutic effect. The addition of anti-CD20 to radiolabeled epratuzumab did not alter epratuzumab’s tissue distribution or tumor uptake.

Conclusions: The combination of an unconjugated anti-CD20 with 90Y-epratuzumab improves anti-tumor responses and may represent an important new treatment strategy for NHL. The mechanism of action of this effect is currently under investigation.

Research Support: USPHS grant P01-CA103985

This Article Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Mattes, M. J. Articles by Goldenberg, D. PubMed Articles by Mattes, M. J. Articles by Goldenberg, D.