Cellular therapy of Epstein-Barr-virus-associated post-transplant lymphoproliferative disease.
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.
Heslop
Helen E
HE
Center for Cell and Gene Therapy, Baylor College of Medicine, The Methodist Hosptial and Texas Children's Hospital, Houston, TX 77030, USA. hheslop@bcm.tmc.edu
Savoldo
Barbara
B
Rooney
Cliona M
CM
D019264:Adoptive Transfer; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D004854:Herpesvirus 4, Human / Q000276:immunology; D006801:Humans; D008232:Lymphoproliferative Disorders / Q000209:etiology / Q000628:therapy* / Q000821:virology; D013601:T-Lymphocytes / Q000276:immunology / Q000637:transplantation