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.
Davis
J E
JE
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
Moss
D J
DJ
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