Epstein-Barr virus (EBV)-associated malignancies offer a unique model to develop T cell-based immune therapies, targeting viral antigens expressed on tumor cells. Throughout the last 15 years, EBV-specific cytotoxic T-lymphocytes (CTL) have been successfully employed for the prophylaxis and treatment of EBV-related lymphoproliferative disorders (LPD) in immunocompromised hosts, particularly after hematopoietic stem cell transplantation. More recently, their use has been extended to treat LPD developing after solid organ transplantation. The favourable experience with LPD has raised interest in applying this therapeutic strategy to other EBV-positive malignancies. Although the preliminary results of T-cell therapy for Hodgkin lymphoma or nasopharyngeal carcinoma have shown the potential for reaching objective responses in patients with advanced-stage cancer, EBV-specific CTLs demonstrated lower efficacy in the treatment of virus-related neoplasia in the immunocompetent host. Thus, further improvements to the protocols employed in the transplantation setting are clearly necessary to increase anti-tumor activity. Promising implementations are underway, including harnessing the therapeutic potential of CTLs specific for subdominant EBV latent cycle epitopes, and delineating strategies aimed at targeting immune evasion mechanisms exerted by tumor cells.
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