Treatment options for post-transplant lymphoproliferative disorder and other Epstein-Barr virus-associated malignancies.
Epstein-Barr virus (EBV) is associated with a range of malignancies that largely arise from a defect in EBV-specific cytotoxic T lymphocyte (CTL) immunity and function. Much work has focused on the reconstitution of CTL immunity to EBV in transplant patients, in whom immunosuppression modalities render them susceptible to post-transplant lymphoproliferative disease (PTLD). Adoptive transfer of autologous CTLs is effective at both preventing and curing PTLD in solid organ transplant recipients and can produce a long-term memory response and protection against recurring disease. In this review, the benefits and restrictions of administering EBV-specific CTLs for the treatment of PTLD are discussed and compared with emerging therapies including the generation of allogeneic human leukocyte antigen-matched CTL banks and the anti-CD20 monoclonal antibody therapy, MabThera. Furthermore, studies involving other EBV-associated disorders have described the potential benefit of adoptive transfer of EBV-specific CTLs for Hodgkin's disease, nasopharyngeal carcinoma, chronic active EBV infection, and Burkitt's lymphoma. The challenges of tailor-making therapies for individual diseases and EBV antigen expression latencies are highlighted, in addition to considering vaccination strategies for optimal treatment.
The EBV Biology Laboratory, Division of Immunology and Infectious Diseases, The Queensland Institute of Medical Research, Post Office, Royal Brisbane Hospital, Brisbane, Queensland 4029, Australia. joanneda@qimr.edu.au
J E
JE
Davis
D J
DJ
Moss
D002051:Burkitt Lymphoma / Q000209:etiology / Q000276:immunology / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D020031:Epstein-Barr Virus Infections / Q000150:complications / Q000276:immunology / Q000473:pathology / Q000628:therapy; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006689:Hodgkin Disease / Q000209:etiology / Q000276:immunology / Q000473:pathology; D006801:Humans; D016219:Immunotherapy, Adoptive; D008232:Lymphoproliferative Disorders / Q000209:etiology / Q000276:immunology / Q000473:pathology / Q000628:therapy; D009303:Nasopharyngeal Neoplasms / Q000209:etiology / Q000276:immunology / Q000473:pathology; D016377:Organ Transplantation / Q000473:pathology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000637:transplantation*; D017735:Virus Latency / Q000276:immunology