Developing immunotherapeutic strategies for the control of Epstein-Barr virus-associated malignancies

Epstein-Barr virus (EBV) infection is associated with various physical huma n malignancies. The potential for immunotherapeutic treatment by cytotoxic T cells (CTL) depends on the degree of EBV-antigen expression, with the bes t prospect revolving around the immunoblastic lymphomas of organ transplant patients in which adoptive transfer of in vitro reactivated CTL has alread y been demonstrated to be effective. Opportunities for effective immunother apy in the treatment of nasopharyngeal carcinoma (NPC) is reduced because t he available targets are limited to relatively nonimmunogenic proteins. How ever, analysis of NPC cells has revealed normal expression of the major his tocompatibility complex (MHC)-encoded peptide transporters TAP-1 and TAP-2, together with high levels of human leukocyte antigen (HLA) class I alleles on the cell surface. Burkitt's lymphoma (BL) displays downregulated expres sion of MHC class I and TAP-1 and TAP-2 proteins, whereas viral antigen exp ression is limited to a protein incapable of processing class I CTL epitope s. It therefore seems likely that effective treatment of BL will revolve ar ound protocols designed to reverse its undifferentiated phenotype.