title: Inhibition of human B-cell lymphoma growth by CD40 stimulation.
abstract: 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.
authors.affiliation: Laboratory of Leukocyte Biology, NCI-FCRDC, MD 21702-1201.
authors.forename: S
authors.initials: S
authors.lastname: Funakoshi
authors.forename: D L
authors.initials: DL
authors.lastname: Longo
authors.forename: M
authors.initials: M
authors.lastname: Beckwith
authors.forename: D K
authors.initials: DK
authors.lastname: Conley
authors.forename: G
authors.initials: G
authors.lastname: Tsarfaty
authors.forename: I
authors.initials: I
authors.lastname: Tsarfaty
authors.forename: R J
authors.initials: RJ
authors.lastname: Armitage
authors.forename: W C
authors.initials: WC
authors.lastname: Fanslow
authors.forename: M K
authors.initials: MK
authors.lastname: Spriggs
authors.forename: W J
authors.initials: WJ
authors.lastname: Murphy
mesh_terms: 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
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D019013:CD40 Antigens; D008562:Membrane Glycoproteins; D023201:CD40 Ligand