Current understanding of the role of Epstein-Barr virus in lymphomagenesis and therapeutic approaches to EBV-associated lymphomas.
A heterogeneous group of malignancies are associated with Epstein-Barr virus (EBV) infection. These malignancies arise in both immunosuppressed and immunocompetent individuals and can be divided into three patterns of latency depending on the viral genes that are expressed. In Type III latency malignancies, such as post-transplant lymphoproliferative disorder (PTLD), EBV has a direct role and the activated B-cell phenotype is characterised by high-level expression of all the immunodominant EBV latency proteins. Thus, EBV-infected B cells are good targets for EBV-specific cytotoxic T lymphocytes (CTLs). New immune-based treatments for PTLD include transfer of ex vivo generated autologous EBV-specific CTLs or, in the case of bone marrow transplant recipients, donor-derived EBV-specific T cells. This strategy could, perhaps, also work in Type II latency malignancies, where EBV acts like a cofactor rather than having a direct role. In initial studies, T cells specific for the weakly immunogenic latent membrane protein 2 have been expanded ex vivo and have promoted tumor regression in a subset of patients. Another potential therapeutic strategy could be to try to induce lytic EBV infection in the tumor cells. This could be done by targeting genes that switch the EBV-infected B cells from the latent to the lytic cycle.
Cohen
Jeffrey I
JI
Medical Virology Section, Laboratory of Clinical Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-1888, USA. jcohen@niaid.nih.gov
Bollard
Catherine M
CM
Khanna
Rajiv
R
Pittaluga
Stefania
S
D019264:Adoptive Transfer; D000998:Antiviral Agents; D020031:Epstein-Barr Virus Infections; D004854:Herpesvirus 4, Human; D006801:Humans; D008223:Lymphoma / Q000209:etiology / Q000628:therapy* / Q000821:virology*
D000998:Antiviral Agents