Immunotherapy of EBVAssociated Malignancies

EBV-associated monoclonal tumors in otherwise immu-nocompetent individuals are known to be mostly invisible from an immunological point of view. In comparison, lymphoproliferative diseases after hematopoetic stem cell transplantation or solid-organ transplantation usually arise as polyclonal proliferations of EBV-infected immortalized cells that are subject to immune control. Immediate partial reconstitution of immune surveillance is the first action to take. Without treatment, benign polyclonal proliferations often progress to oligoclonality or monoclonality with greatly reduced chances for successful therapy.

New immunotherapeutic approaches[14] aim at the elimination of B cells through monoclonal antibodies such as anti-CD20, anti-CD21, or anti-CD24. Alternatively, EBV-specific cytotoxic T cells (CTL), which are generated in vitro by cocultivation of donor-derived T cells with EBV-infected B-lymphoblastoid cells, are adoptively transferred in the otherwise immunosuppressed recipients in the case of a developing LPD.

Depletion of B cells and adoptive transfer of T cells are often complemented by the administration of interferons IFN-g and IFN-a or in vivo blocking of interleukin IL-6 by the addition of anti-IL-6 antibody resulting in remission and prolonged survival of some cases.

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