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 have been explored as prophylaxis and therapy for EBV-associated malignancies for more than two decades. EBV-specific T cells 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 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 that express a limited array of latent EBV antigens (type 2 latency),.
Several approaches are actively being pursued to improve the antitumor activity of EBV-specific T cells including activation and expansion of T cells specific for the EBV antigens expressed in type 2 latency, genetic approaches to render EBV-specific T cells 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 EBV-specific T cells will become an integral part of treatment armamentarium against EBV-positive malignancies in the near future.
Gottschalk S et al. Adoptive T-cell Immunotherapy. Current topics in microbiology and immunology. 2015;391:427-454.
Chia WK et al. Adoptive T-cell transfer and chemotherapy in the first-line treatment of metastatic and/or locally recurrent nasopharyngeal carcinoma. Mol Ther. 2014;22(1):132–139.