Adoptive T-cell therapy for Epstein-Barr virus-positive Hodgkin's disease

Immunotherapy approaches with antigen-specific cytotoxic T lymphocytes (CTLs) have proved safe and effective prophylaxis and treatment of Epstein-Barr virus (EBV)-associated lymphomas arising after bone marrow transplantation. EBV is also associated with other malignancies including about 40% of cases of Hodgkin's disease making this tumor another potential target for EBV-targeted immunotherapy. While studies with autologous EBV-specific CTLs have shown antiviral activity and immune effects, the clinical responses have been less impressive than those observed in post-transplant lymphomas. There are several possible reasons why the malignant cells in EBV-positive Hodgkin's disease may be less susceptible to immunotherapy approaches, including the fact that they express a more restricted array of EBV-encoded antigens and possess many immune evasion strategies. A number of approaches to overcome these tumor evasion strategies including targeting CTLs to the expressed antigens and genetic modification of CTLs are being evaluated.