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Depletion of B cells in vivo by a chimeric mouse human monoclonal antibody
to CD20
ME Reff, K Carner, KS Chambers, PC Chinn, JE Leonard, R Raab, RA Newman, N Hanna and DR Anderson
IDEC Pharmaceuticals Corporation, San Diego, CA 92121.
Murine monoclonal antibody 2B8 specifically recognizes the CD20
phosphoprotein expressed on the surface of normal B lymphocytes and B- cell
lymphomas. The light- and heavy-chain variable regions of 2B8 were cloned,
after amplification by the polymerase chain reaction, into a cDNA
expression vector that contained human IgG1 heavy chain and human
kappa-light chain constant regions. High-level expression of chimeric- 2B8
antibody (C2B8) was obtained in Chinese hamster ovary cells. Purified C2B8
exhibited antigen binding affinity and human-tissue reactivity similar to
the native murine antibody. In vitro studies showed the ability of C2B8 to
bind human C1q, mediate complement- dependent cell lysis of human
B-lymphoid cell lines, and lyse human target cells through
antibody-dependent cellular cytotoxicity. Infusion of macaque cynomolgus
monkeys with doses ranging from 1.6 mg/kg to 6.4 mg/kg resulted in greater
than 98% depletion of peripheral blood (PB) B cells and 40% to 70%
depletion of lymph node B cells. Recovery of PB B cells usually started at
2 weeks after treatment and required 60 to greater than 90 days to reach
normal levels. As much as 95% depletion of B cells in peripheral lymph
nodes and bone marrow was observed following weekly injections of 16.8
mg/kg antibody. No toxicity was observed in any of the animals. These
results offer the possibility of using an "immunologically active" chimeric
anti-CD20 antibody as an alternative approach in the treatment of B-cell
lymphoma.
Volume 83,
Issue 2,
pp. 435-445,
01/15/1994
Copyright © 1994 by The American Society of Hematology
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