Epstein-Barr virus (EBV) is associated with a range of
malignancies involving B cells, T cells, natural killer (NK) cells, epithelial cells, and smooth muscle. All of these are associated with the latent life cycles of EBV, but the pattern of latency-associated
viral antigens expressed in
tumor cells depends on the type of
tumor. EBV-specific T cells (EBVSTs) have been explored as prophylaxis and
therapy for EBV-associated
malignancies for more than two decades. EBVSTs have been most successful as prophylaxis and
therapy for post-transplant lymphoproliferative disease (PTLD) , which expresses the full array of latent EBV
antigens (type 3 latency), in hematopoietic stem-cell transplant (HSCT) recipients. While less effective, clinical studies have also demonstrated their therapeutic potential for PTLD post-solid organ transplant and for EBV-associated
malignancies such as
Hodgkin's lymphoma,
non-Hodgkin's lymphoma, and
nasopharyngeal carcinoma (NPC) that express a limited array of latent EBV
antigens (type 2 latency). Several approaches are actively being pursued to improve the antitumor activity of EBVSTs including activation and expansion of T cells specific for the EBV
antigens expressed in type 2 latency, genetic approaches to render EBVSTs resistant to the immunosuppressive
tumor environment, and combination approaches with other immune-modulating modalities. Given the recent advances and renewed interest in
cell therapy, we hope that EBVSTs will become an integral part of our treatment armamentarium against EBV-positive
malignancies in the near-future.