Sensitivity of Epstein-Barr virus-induced B cell tumor to apoptosis mediated by anti-CD95/Apo-1/fas antibody.
Epstein-Barr virus (EBV) can induce uncontrolled B lymphocyte proliferation leading to fatal lymphoma in immunocompromised patients. The sensitivity to apoptosis of B lymphoid cell lines (LCL) derived from EBV-induced lymphoproliferative disorders was investigated. In vitro and in vivo, these B LCL strongly express CD95/Apo-1/fas antigen and undergo apoptosis upon stimulation with anti-Apo-1 monoclonal antibody. When inoculated into severe-combined immunodeficient (scid) mice, human B cells lines developed into rapidly growing tumors. Administration of an agonistic anti-Apo-1 antibody significantly delayed tumor progression. Relapses were frequent, but were not caused by selection of resistant B cells, since B cells from relapsing tumors underwent apoptosis on re-exposure. Induction of apoptosis by an anti-C95/Apo-1/fas-specific antibody could be applied for therapy of EBV-induced B cell tumors and contribute to our understanding of the mechanisms of T cell-mediated elimination of EBV lymphomas in immunodeficient patients.
Durandy
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Institut National de la Santé et de la Recherche Médicale U 429, Hôpital Necker-Enfants Malades, Paris, France. durandy@ceylan.necker. fr
Le Deist
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Emile
J F
JF
Debatin
K
K
Fischer
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A
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects* / Q000276:immunology*; D004854:Herpesvirus 4, Human / Q000472:pathogenicity*; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D016393:Lymphoma, B-Cell / Q000209:etiology* / Q000628:therapy*; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation / Q000276:immunology; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000276:immunology*
D000911:Antibodies, Monoclonal; D019014:fas Receptor