Inhibition of human B-cell lymphoma growth by CD40 stimulation.
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.
Funakoshi
S
S
Laboratory of Leukocyte Biology, NCI-FCRDC, MD 21702-1201.
Longo
D L
DL
Beckwith
M
M
Conley
D K
DK
Tsarfaty
G
G
Tsarfaty
I
I
Armitage
R J
RJ
Fanslow
W C
WC
Spriggs
M K
MK
Murphy
W J
WJ
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D015703:Antigens, CD / Q000032:analysis / Q000502:physiology*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000032:analysis / Q000502:physiology*; D019013:CD40 Antigens; D023201:CD40 Ligand; D002455:Cell Division; D006801:Humans; D016393:Lymphoma, B-Cell / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D008562:Membrane Glycoproteins / Q000494:pharmacology; D051379:Mice; D016513:Mice, SCID; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D019013:CD40 Antigens; D008562:Membrane Glycoproteins; D023201:CD40 Ligand