Epstein Barr virus-associated lymphoproliferative diseases: the virus as a therapeutic target

• Published in: Experimental & molecular medicine Vol. 47; no. 1; p. e136
• Main Authors: Tse, Eric, Kwong, Yok-Lam
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-01-2015; Springer Nature B.V; Nature Publishing Group
• Subjects: 692/699/1541/1990/291/1621/1915; Antiviral Agents - therapeutic use; Biomedical and Life Sciences; Biomedicine; Cell- and Tissue-Based Therapy; DNA Methylation; Epstein-Barr virus; Epstein-Barr Virus Infections - complications; Genome, Viral; Hematopoietic Stem Cell Transplantation; Herpesvirus 4, Human - physiology; Humans; Immunotherapy, Adoptive; Lymphoproliferative Disorders - diagnosis; Lymphoproliferative Disorders - etiology; Lymphoproliferative Disorders - therapy; Medical Biochemistry; Molecular Medicine; Organ Transplantation - adverse effects; Review; Stem Cells; T-Lymphocytes - immunology; Transplantation, Homologous; Virus Latency
• ISSN: 2092-6413; 1226-3613; 2092-6413
• DOI: 10.1038/emm.2014.102

Epstein Barr virus (EBV)-associated lymphoproliferative diseases (LPDs) express all EBV latent antigens (type III latency) in immunodeficient patients and limited antigens (type I and II latencies) in immunocompetent patients. Post-transplantation lymphoproliferative disease (PTLD) is the prototype exhibiting type III EBV latency. Although EBV antigens are highly immunogenic, PTLD cell proliferation remains unchecked because of the underlying immunosuppression. The restoration of anti-EBV immunity by EBV-specific T cells of either autologous or allogeneic origin has been shown to be safe and effective in PTLDs. Cellular therapy can be improved by establishing a bank of human leukocyte antigen-characterized allogeneic EBV-specific T cells. In EBV+ LPDs exhibiting type I and II latencies, the use of EBV-specific T cells is more limited, although the safety and efficacy of this therapy have also been demonstrated. The therapeutic role of EBV-specific T cells in EBV+ LPDs needs to be critically reappraised with the advent of monoclonal antibodies and other targeted therapy. Another strategy involves the use of epigenetic approaches to induce EBV to undergo lytic proliferation when expression of the viral thymidine kinase renders host tumor cells susceptible to the cytotoxic effects of ganciclovir. Finally, the prophylactic use of antiviral drugs to prevent EBV reactivation may decrease the occurrence of EBV+ LPDs.
Blood cancer: Fighting the Epstein-Barr virus
Cellular therapies, which use living cells to treat disease, could be useful against cancers associated with Epstein-Barr virus (EBV). Best-known for causing glandular fever, EBV is also implicated in many malignant "lymphoproliferative" conditions, in which white blood cells multiply excessively. Yok-Lam Kwong and Eric Tse of Queen Mary Hospital in Hong Kong have reviewed the advantages and disadvantages of several forms of cellular therapy, which utilize healthy white blood cells from donors or from patients themselves to combat EBV. Such treatment has proven to be safe and effective, especially in patients with immunity suppressed by diseases or drugs. The availability of cellular therapy could be widened by establishing a bank of suitable cells. Its efficacy needs to be evaluated against emerging alternatives including antibodies and drugs.