ABSTRACT
Summary 1579 Introduction 1579 Epstein-Barr virus-based therapeutic approaches 1580 Enhancement of the immune response to 1581
viral proteins Epstein-Barr virus vaccination 1582 Inhibition of Epstein-Barr virus transforming genes 1583
Elimination of Epstein-Barr virus episomes 1584 Epigenetic targets 1584 Epstein-Barr virus-dependent expression of 1585
toxic/apoptotic genes Induction of the lytic cycle 1585 Key points 1587 References 1587
The association of viruses with several human tumors has now clearly been established. The most common viruses associated with lymphomas are the herpesviruses. Epstein-Barr virus (EBV), a gammaherpesvirus, is widely distributed in all human populations and persists in the individuals as a lifelong, asymptomatic infection of B cells. Apart from this ubiquity, EBV is causative and/or associated with a growing number of benign and malignant lymphoid and epithelial diseases. These include infectious mononucleosis, oral hairy leukoplakia, post-transplant B cell proliferations, Burkitt lymphoma, nasopharyngeal carcinomas, Hodgkin lymphomas, and others. Epstein-Barr virus adopts different forms of latent infection, defined by the restricted pattern of genes expressed (latency I, II, III) in different tumor types and reflecting the complex interaction between the virus and the host cell. Regardless of the role of the virus in the pathogenesis of these diseases (which remains to be completely elucidated), the virus itself represents a target par excellence for designing tumorselective therapeutic approaches. The presence of the EBV genome in virtually all tumor cells stands in contrast to the rare infection of normal cells, ensuring that EBV-targeted therapeutic approaches will have a high specificity and a low toxicity. In this chapter we review all developing strategies that use EBV as a target to mediate tumor cell death in EBV-associated malignancies. Several pharmacologic and
immunotherapeutic approaches to treat or prevent EBVassociated tumors are at varying levels of clinical studies. These strategies are all based on altering viral gene expression to render the EBV-positive tumor cells sensitive to antiviral drugs, and commit to initiate the replicative cycle, utilizing its own lytic potential to kill the host tumor cell or, alternatively, the altered gene expression allows the tumor cells to bypass immune evasion strategies of the virus and become a target that is on the radar of the host cellular immune system.
