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Inhibition of human B-cell lymphoma growth by CD40 stimulation
S Funakoshi, DL Longo, M Beckwith, DK Conley, G Tsarfaty, I Tsarfaty, RJ Armitage, WC Fanslow, MK Spriggs and WJ Murphy
Laboratory of Leukocyte Biology, NCI-FCRDC, MD 21702-1201.
CD40 is a molecule present on B lymphocyte lineage cells that is important
in B-cell differentiation and activation. Signaling through CD40 has been
shown to exert costimulatory signals on normal B cells resulting in
proliferative and differentiation responses. Examination of several B-cell
lymphomas showed cell-surface expression of the CD40 molecule. Incubation
of these lymphomas with anti-CD40 antibodies resulted in significant growth
inhibition in vitro. Cross-linking of the CD40 antibodies resulted in even
greater inhibition of proliferation. A recombinant soluble human CD40
ligand was also shown to inhibit lymphoma proliferation. When various human
B-cell lymphomas were transferred into mice with severe combined immune
deficiency, the treatment of the mice with anti-CD40 antibodies resulted in
significant increases in survival showing that anti-CD40 is efficacious
after in vivo administration. Thus, CD40 stimulation by either the antibody
or soluble ligand directly inhibits human B-cell lymphoma growth and
therefore, may be of significant clinical use in their treatment.
Volume 83,
Issue 10,
pp. 2787-2794,
05/15/1994
Copyright © 1994 by The American Society of Hematology
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