Epstein-Barr virus-specific cytotoxic T-lymphocytes for adoptive immunotherapy of post-transplant lymphoproliferative disease

Abstract

Post-transplant lymphoproliferative disease (PTLD) refers to a collection of clinically and pathologically diverse tumours associated with iatrogenic immunosuppression following transplantation. In most cases, tumourigenesis results from a deficit in Epstein-Barr virus (EBV)-specific cytotoxic T-lymphocyte (CTL) activity that leads to uncontrolled EBV-driven outgrowth of latently infected B-lymphocytes. Conventional treatment for PTLD typically involves a reduction in immunosuppression, but this approach is frequently unsuccessful and mortality remains high. An alternative, adoptive immunotherapy, involving the administration of EBV-specific CTLs cultured in vitro has been developed with the aim of selectively reconstituting EBV-directed immunity and effecting targeted tumour destruction. This approach has been the subject of several clinical studies, and these provide encouraging evidence of its clinical efficacy. This review presents an overview of the pathogenesis of PTLD and examines current progress in the use of adoptive immunotherapy for its treatment.