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

Epstein-Barr virus (EBV) infection is associated with various physical human malignancies. The potential for immunotherapeutic treatment by cytotoxic T cells (CTL) depends on the degree of EBV-antigen expression, with the best prospect revolving around the immunoblastic lymphomas of organ transplant patients in which adoptive transfer of in vitro reactivated CTL has already been demonstrated to be effective. Opportunities for effective immunotherapy in the treatment of nasopharyngeal carcinoma (NPC) is reduced because the available targets are limited to relatively nonimmunogenic proteins. However, analysis of NPC cells has revealed normal expression of the major histocompatibility 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 expression of MHC class I and TAP-1 and TAP-2 proteins, whereas viral antigen expression is limited to a protein incapable of processing class I CTL epitopes. It therefore seems likely that effective treatment of BL will revolve around protocols designed to reverse its undifferentiated phenotype.