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Retention of B-cell-specific monoclonal antibodies by human lymphoma cells
OW Press, J Howell-Clark, S Anderson and I Bernstein
Department of Medicine, University of Washington, Seattle.
The rates of endocytosis, intracellular degradation, and cell-surface
shedding of 125I-labeled monoclonal antibodies (MoAbs) HD-37 (anti- CD19),
B1 (anti-CD20), MB-1 (anti-CD37), BC8 (anti-CD45), and DA4-4 (anti-mu) by
B-lymphoma cells were compared by cellular radioimmunoassay,
ultrastructural autoradiography, sodium dodecyl sulfate-polyacrylamide gel
electrophoresis, and thin layer chromatography using biopsy specimens from
12 patients with non- Hodgkin's lymphomas. 125I-BC8 was stably retained on
the surface of lymphoma cells without appreciable internalization or
shedding, whereas 125I-DA4-4 underwent rapid endocytosis and degradation.
125I-B1 was not internalized or degraded by tumor cells, but rapidly
dissociated from the cell surface in intact form. Moderate rates of
endocytosis, intracellular metabolism, and cell-surface shedding were shown
by 125I- HD37 and 125I-MB-1. The 3 patients with diffuse, small
cleaved-cell lymphomas internalized and degraded antibodies more slowly
than did patients with other histologic subtypes. These kinetic differences
may be important in the selection of MoAbs for immunotoxin and
radioimmunoconjugate therapy of B-cell malignancies.
Volume 83,
Issue 5,
pp. 1390-1397,
03/01/1994
Copyright © 1994 by The American Society of Hematology
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