Sensitivity of Epstein‐Barr virus‐induced B cell tumor to apoptosis mediated by anti‐CD95/Apo‐1/fas antibody

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Abstract
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 lymphopro‐liferative 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.