Immunotherapy targeting EBV-expressing lymphoproliferative diseases

Epstein-Barr virus (EBV) is associated with non-Hodgkin's lymphoma (NHL), occurring in immunocompetent individuals as well as those with immunodeficiency. In patients with immunodeficiency, the nature of EBV infection in the malignant cell determines the pattern of antigen expression and the associated presence of targets for cellular immunotherapy. EBV-expressing lymphoma cells in the setting of immunodeficiency express type III latency, characterized by expression of all nine latent-cycle EBV antigens, and strategies to restore EBV-specific immune responses have resulted in effective anti-tumour activity. In contrast, EBV-associated NHL in immunocompetent individuals is characterized by type II latency, where a more restricted array of EBV-associated antigens is expressed. In this setting, T-cell therapies are limited by inadequate persistence of transferred T cells and by tumour-evasion strategies. A number of strategies to genetically modify the infused T cells and modulate the host environment are under evaluation.

Key words: EBV, post-transplant lymphoproliferative disease, cytotoxic T lymphocytes, chimeric antigen receptors