Effects of CD40 stimulation in the prevention of human EBV-lymphomagenesis.
CD40 is a molecule present on B lineage cells, both normal and neoplastic. Signalling through CD40 has been demonstrated to promote B cell growth and differentiation in vitro. In contrast to its effects on normal B cells, we have found that CD40 stimulation can inhibit the growth of various aggressive histology human B cell lymphomas both in vitro and in vivo. Moreover, using a human/mouse chimera model in which human EBV-induced B cell lymphomas can spontaneously arise, we have found that CD40 stimulation an prevent the occurrence of this human lymphoma in mice. However, normal human B cell engraftment and function was not adversely affected in these mice by CD40 stimulation. This indicates that CD40 stimulation is selective in its effects on aggressive histology B cell lymphomas. Thus, CD40 stimulation either by antibody or a recombinant soluble ligand, may be of potential clinical use, not only in the treatment of EBV-induced B cell lymphomas, but also in their prevention.
Funakoshi
S
S
Jikei University School of Medicine, Tokyo, Japan.
Taub
D D
DD
Asai
O
O
Hirano
A
A
Ruscetti
F W
FW
Longo
D L
DL
Murphy
W J
WJ
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000951:Antigens, Neoplasm / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000637:transplantation / Q000821:virology; D019013:CD40 Antigens / Q000276:immunology*; D023201:CD40 Ligand; D002472:Cell Transformation, Viral / Q000187:drug effects; D002678:Chimera; D006566:Herpesviridae Infections / Q000276:immunology* / Q000628:therapy; D004854:Herpesvirus 4, Human / Q000472:pathogenicity*; D006801:Humans; D016393:Lymphoma, B-Cell / Q000276:immunology / Q000517:prevention & control* / Q000628:therapy / Q000821:virology; D008228:Lymphoma, Non-Hodgkin / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D014407:Tumor Cells, Cultured; D014412:Tumor Virus Infections / Q000276:immunology* / Q000628:therapy
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D019013:CD40 Antigens; D008562:Membrane Glycoproteins; D023201:CD40 Ligand