Adoptive immunotherapy for EBV-associated malignancies

Latent Epstein-Barr virus (EBV) infection is associated with a diverse group of malignancies including Burkitt's lymphoma, Hodgkin's disease, nasopharyngeal carcinoma (NPC), and lymphoproliferative disease (LPD). EBV proteins expressed in these malignancies provide targets for the adoptive immunotherapy with antigen-specific cytotoxic T cells (CTL) and EBV-specific CTL have been used successfully for the prophylaxis and treatment of EBV-LPD post hematopoietic stem cell transplantation (HSCT). The clinical experience with EBV-specific CTL for other EBV-associated malignancies such as Hodgkin's disease and NPC is limited and the results obtained so far indicate that EBV-specific CTL are less effective than for EBV-LPD post HSCT. Decreased CTL efficacy most likely reflect immune evasion strategies by tumor cells such as down regulation of immunodominant EBV proteins and secretion of inhibitory cytokines. To overcome these immune evasion strategies a number of approaches have been developed including targeting CTL to subdominant EBV antigens and genetically modifying CTL to increase their potency.