Immunotherapy for Epstein-Barr virus-associated tumors

Abstract

Epstein-Barr Virus (EBV) is associated with a number of tumors, including lymphomas in solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) recipients, patients with the acquired immunodeficiency syndrome (AIDS), Burkitt's lymphoma, as well as a subset of patients with nasopharyngeal carcinoma (NPC) and Hodgkin's disease (HD). The types of latent EBV infections vary in these tumors, which influences the EBV antigens expressed and ultimately the immunogenicity of tumor cells. Not all EBV associated malignancies are directly related to altered cellular immunity, as is the case with EBV induced lymphoproliferations in immunocompromised patients. Treatment strategies have ranged from restoration of normal cellular immunity, which is generally successful in SOT and HSCT patients, anti-B cell monoclonal antibodies, and conventional chemotherapy and radiation. The fact that these tumors express EBV antigens for which many individuals have high circulating levels of protective cytotoxic T lymphocytes (CTL) has lead to investigation into the applicability of adoptive transfer of EBV specific T cells. Initial success with adoptive immunotherapy for HSCT and SOT patients has lead to current studies examining the feasibility and efficacy of this strategy for other EBV associated tumors, such as NPC and HD. We will review the pathogenesis of these disorders, current therapies, and future investigations aimed at targeting EBV antigen expression on these tumors.