Cellular therapy of Epstein-Barr-virus-associated post-transplant lymphoproliferative disease

Abstract

During the immunodeficiency that follows hemopoietic stem cell transplant or solid organ transplant, lymphoproliferation can develop due to uncontrolled expansion of Epstein-Barr-virus (EBV)-infected B cells that express the full spectrum of EBV latent antigens. As development of post-transplant lymphoproliferative disease (PTLD) in these patients is clearly associated with a deficient EBV-specific cellular immune response, immunotherapy strategies to restore the EBV-specific immune response have been evaluated. In hemopoietic stem cell transplant recipients, adoptively transferred donor-derived EBV-specific T cells have been able to restore immunity and eradicate overt lymphoproliferation. Autologous or closely matched allogeneic EBV-specific cytotoxic T lymphocytes have also shown promise in recipients of solid organ transplant. The use of genetically modified T cells or newer suicide genes may result in improved safety and efficacy. Current challenges are to define indications for immunotherapy or antibody therapy in patients with incipient or overt PTLD.