EBV-related lymphomas: New approaches to treatment

Current Treatment Options in Oncology

Volumn 14, Issue 2, 2013, Pages 224-236

  Kanakry, Jennifer A ^a   Ambinder, Richard F ^a  

^a JOHNS HOPKINS UNIVERSITY   (United States)

Author keywords

Adoptive T cell therapy; Burkitt lymphoma; Epstein Barr virus; Epstein Barr virus DNA; Epstein Barr virus specific cytotoxic T cells; HIV associated lymphomas; Hodgkin lymphoma; Immunodeficiency; Non Hodgkin lymphoma; Posttransplantation lymphoproliferative disorder; Rituximab; Viral latency

Indexed keywords

8 [4 (1 AMINOCYCLOBUTYL)PHENYL] 9 PHENYL 1,2,4 TRIAZOLO[3,4 F][1,6]NAPHTHYRIDIN 3(2H) ONE; ALEMTUZUMAB; ANTIMETABOLITE; ANTIRETROVIRUS AGENT; ARSENIC TRIOXIDE; AZACITIDINE; BORTEZOMIB; CALCINEURIN INHIBITOR; DASATINIB; EPSTEIN BARR VIRUS VACCINE; GANCICLOVIR; GEMCITABINE; HISTONE DEACETYLASE INHIBITOR; LIVE VACCINE; MAMMALIAN TARGET OF RAPAMYCIN INHIBITOR; OKT 3; PARTHENOLIDE; PROTEIN KINASE SYK INHIBITOR; RAPAMYCIN; RECOMBINANT GLYCOPROTEIN GP350 VACCINE; RECOMBINANT PROTEIN; RECOMBINANT VACCINE; RITUXIMAB; STEROID; THYMOCYTE ANTIBODY; UNCLASSIFIED DRUG; UNINDEXED DRUG; VALPROIC ACID; VIRUS ANTIGEN; VIRUS DNA; VIRUS PROTEIN;

ACQUIRED IMMUNE DEFICIENCY SYNDROME; ADOPTIVE IMMUNOTHERAPY; ADVANCED CANCER; ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION; ARTICLE; BIOLOGICAL MONITORING; CANCER CHEMOTHERAPY; CANCER REGRESSION; CANCER SURGERY; CELL THERAPY; CHRONIC LYMPHATIC LEUKEMIA; COST BENEFIT ANALYSIS; COST EFFECTIVENESS ANALYSIS; CYTOTOXIC T LYMPHOCYTE; DIET THERAPY; DISEASE ASSOCIATION; DONOR LYMPHOCYTE INFUSION; DRUG CONTRAINDICATION; DRUG COST; DRUG EFFICACY; DRUG HYPERSENSITIVITY; DRUG MECHANISM; DRUG POTENTIATION; EPSTEIN BARR VIRUS; EPSTEIN BARR VIRUS INFECTION; EPSTEIN BARR VIRUS RELATED LYMPHOMA; GRAFT VERSUS HOST REACTION; HIGHLY ACTIVE ANTIRETROVIRAL THERAPY; HISTOPATHOLOGY; HODGKIN DISEASE; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; IMMUNE RESPONSE; IMMUNOGLOBULIN DEFICIENCY; IMMUNOSUPPRESSIVE TREATMENT; LIFESTYLE MODIFICATION; LYMPHOMA; LYMPHOMA CELL; MACROPHAGE; MONOTHERAPY; NEUTROPENIA; NONHODGKIN LYMPHOMA; NONHUMAN; ORGAN TRANSPLANTATION; POSTTRANSPLANT LYMPHOPROLIFERATIVE DISEASE; REGULATORY T LYMPHOCYTE; SIGNAL TRANSDUCTION; TREATMENT RESPONSE; VIRUS CELL INTERACTION; VIRUS GENE; VIRUS REPLICATION;

ANTIGENS, VIRAL; ANTINEOPLASTIC AGENTS; ANTIVIRAL AGENTS; CLINICAL TRIALS, PHASE I AS TOPIC; CLINICAL TRIALS, PHASE II AS TOPIC; EPSTEIN-BARR VIRUS INFECTIONS; HERPESVIRUS 4, HUMAN; HUMANS; IMMUNOTHERAPY, ADOPTIVE; LYMPHOMA; T-LYMPHOCYTES, CYTOTOXIC; T-LYMPHOCYTES, REGULATORY; VIRAL VACCINES; VIRUS LATENCY; VIRUS REPLICATION;

EID: 84877771295     PISSN: 15272729     EISSN: 15346277     Source Type: Journal    
DOI: 10.1007/s11864-013-0231-y     Document Type: Article

References (72)

1. Levin LI, Chang ET, Ambinder RF, et al. Atypical prediagnosis Epstein-Barr virus serology restricted to EBV-positive Hodgkin lymphoma. Blood. 2012;120:3750-5.
2. Jones K, Nourse JP, Keane C, et al. Tumor-specific but not nonspecific cell-free circulating DNA can be used to monitor disease response in lymphoma. Am J Hematol. 2012;87:258-65.
3. Wang ZY, Liu QF, Wang H, et al. Clinical implications of plasma Epstein-Barr virus DNA in early-stage extranodal nasal-type NK/T-cell lymphoma patients receiving primary radiotherapy. Blood. 2012;120:2003-10. Elevated pre-treatment EBV-DNA copy number in plasma is associated with inferior survival outcomes in extranodal NK/T-cell lymphoma.
4. Gandhi MK, Lambley E, Burrows J, et al. Plasma Epstein-Barr virus (EBV) DNA is a biomarker for EBV-positive Hodgkin's lymphoma. Clin Cancer Res. 2006;12:460-4.
5. Kanakry JA, Li H, Gellert LL, et al. Plasma Epstein-Barr virus DNA as a marker of tumor response in Hodgkin lymphoma. 2012: Abstract #8003. Plasma EBV-DNA correlates well with EBV tumor status and pre-treatment plasma EBV-DNA positivity is an independent prognostic marker of inferior progression-free survival in Hodgkin lymphoma.
6. Hohaus S, Santangelo R, Giachelia M, et al. The viral load of Epstein-Barr virus (EBV) DNA in peripheral blood predicts for biological and clinical characteristics in Hodgkin lymphoma. Clin Cancer Res. 2011;17:2885-92. High plasma EBV-DNA correlates with tumor-infiltrating macrophages in Hodgkin lymphoma.
7. Styczynski J, Reusser P, Einsele H, et al. Management of HSV, VZV and EBV infections in patients with hematological malignancies and after SCT: guidelines from the Second European Conference on Infections in Leukemia. Bone Marrow Transplant. 2009;43:757-70.
8. Ito Y, Kimura H, Maeda Y, et al. Pretreatment EBV-DNA copy number is predictive of response and toxicities to SMILE chemotherapy for extranodal NK/T-cell lymphoma, nasal type. Clin Cancer Res. 2012;18:4183-90. Plasma EBV-DNA copy number predicts response to chemotherapy and grade 4 toxicity for patients with extranodal NK/T-cell lymphoma.
9. Kasamon YL, Jacene HA, Gocke CD, et al. Phase 2 study of rituximab-ABVD in classical Hodgkin lymphoma. Blood. 2012;119:4129-32.
10. Styczynski J, Einsele H, Gil L, Ljungman P. Outcome of treatment of Epstein-Barr virus-related post-transplant lymphoproliferative disorder in hematopoietic stem cell recipients: a comprehensive review of reported cases. Transpl Infect Dis. 2009;11:383-92.
11. Kim JH, Kim WS, Park C. Epstein-Barr virus latent membrane protein-1 protects B-cell lymphoma from rituximab-induced apoptosis through miR-155-mediated Akt activation and up-regulation of Mcl-1. Leuk Lymphoma. 2012;53:1586-91. Role of Akt pathway in LMP-1-mediated rituximab resistance in EBV-positive lymphomas.
12. Nelson BP, Wolniak KL, Evens A, Chenn A, Maddalozzo J, Proytcheva M. Early posttransplant lymphoproliferative disease: clinicopathologic features and correlation with mTOR signaling pathway activation. Am J Clin Pathol. 2012;138:568-78. mTOR activation in EBV-PTLD.
13. El-Salem M, Raghunath PN, Marzec M, et al. Constitutive activation of mTOR signaling pathway in post-transplant lymphoproliferative disorders. Lab Invest. 2007;87:29-39.
14. Gibelli NE, Tannuri U, Pinho-Apezzato ML, et al. Sirolimus in pediatric liver transplantation: a single-center experience. Transplant Proc. 2009;41:901-3.
15. Garcia VD, Bonamigo Filho JL, Neumann J, et al. Rituximab in association with rapamycin for post-transplant lymphoproliferative disease treatment. Transpl Int. 2003;16:202-6.
16. Vaysberg M, Balatoni CE, Nepomuceno RR, Krams SM, Martinez OM. Rapamycin inhibits proliferation of Epstein-Barr virus-positive B-cell lymphomas through modulation of cell-cycle protein expression. Transplantation. 2007;83:1114-21.
17. Heslop HE, Slobod KS, Pule MA, et al. Long-term outcome of EBV-specific T-cell infusions to prevent or treat EBV-related lymphoproliferative disease in transplant recipients. Blood. 2010;115:925-35. Long-term outcomes of EBV-specific CTL therapy for the prevention and treatment of EBV-PTLD.
18. Rooney CM, Smith CA, Ng CYC, et al. Use of Gene-Modified Virus-Specific T-Lymphocytes to Control Epstein-Barr-Virus-Related Lymphoproliferation. Lancet. 1995;345:9-13.
19. Bollard CM, Rooney CM, Heslop HE. T-cell therapy in the treatment of post-transplant lymphoproliferative disease. Nat Rev Clin Oncol. 2012;9:510-9. Review of EBV-CTL therapies.
20. Doubrovina E, Oflaz-Sozmen B, Prockop SE, et al. Adoptive immunotherapy with unselected or EBV-specific T cells for biopsy-proven EBV+ lymphomas after allogeneic hematopoietic cell transplantation. Blood. 2012;119:2644-56. Comparison of clinical outcomes following donor lymphocyte infusion versus EBV-CTL therapy for post-HSCT EBV-PTLD.
21. Haque T, Wilkie GM, Jones MM, et al. Allogeneic cytotoxic T-cell therapy for EBV-positive posttransplantation lymphoproliferative disease: results of a phase 2 multicenter clinical trial. Blood. 2007;110:1123-31.
22. Icheva V, Kayser S, Wolff D, et al. Adoptive transfer of Epstein-Barr Virus (EBV) nuclear antigen 1-specific T cells as treatment for EBV reactivation and lymphoproliferative disorders after allogeneic stem-cell transplantation. J Clin Oncol 2012. Interferon-gamma capture technique for rapid isolation of EBV-CTLs.
23. Feuchtinger T, Opherk K, Bethge WA, et al. Adoptive transfer of pp 65-specific T cells for the treatment of chemorefractory cytomegalovirus disease or reactivation after haploidentical and matched unrelated stem cell transplantation. Blood. 2010;116:4360-7.
24. Gerdemann U, Keirnan JM, Katari UL, et al. Rapidly generated multivirus-specific cytotoxic T lymphocytes for the prophylaxis and treatment of viral infections. Mol Ther. 2012;20:1622-32. Use of synthetic peptides and cytokines to facilitate the rapid expansion of multi-virus-specific CTLs.
25. De Angelis B, Dotti G, Quintarelli C, et al. Generation of Epstein-Barr virus-specific cytotoxic T lymphocytes resistant to the immunosuppressive drug tacrolimus (FK506). Blood. 2009;114:4784-91.
26. Brewin J, Mancao C, Straathof K, et al. Generation of EBV-specific cytotoxic T cells that are resistant to calcineurin inhibitors for the treatment of posttransplantation lymphoproliferative disease. Blood. 2009;114:4792-803.
27. Quintarelli C, Savoldo B, Dotti G. Gene therapy to improve function of T cells for adoptive immunotherapy. Methods Mol Biol. 2010;651:119-30.
28. Marin V, Cribioli E, Philip B, et al. Comparison of different suicide gene strategies for the safety improvement of genetically manipulated T cells. Hum Gene Ther Methods 2012.
29. He J, Tang XF, Chen QY, et al. Ex vivo expansion of tumor-infiltrating lymphocytes from nasopharyngeal carcinoma patients for adoptive immunotherapy. Chin J Cancer. 2012;31:287-94.
30. Louis CU, Straathof K, Bollard CM, et al. Enhancing the in vivo expansion of adoptively transferred EBV-specific CTL with lymphodepleting CD45 monoclonal antibodies in NPC patients. Blood. 2009;113:2442-50.
31. Perna SK, De Angelis B, Pagliara D, et al. Interleukin 15 provides relief to cytotoxic T lymphocytes from regulatory T cell-mediated inhibition: implications for adoptive T-cell based therapies of lymphoma. Clin Cancer Res 2012. Role of IL-15 in promoting the survival and expansion of EBV-CTLs in the presence of regulatory T-cells.
32. Foster AE, Dotti G, Lu A, et al. Antitumor activity of EBV-specific T lymphocytes transduced with a dominant negative TGF-beta receptor. J Immunother. 2008;31:500-5.
33. Ouyang J, Juszczynski P, Rodig SJ, et al. Viral induction and targeted inhibition of galectin-1 in EBV+ posttransplant lymphoproliferative disorders. Blood. 2011;117:4315-22. Role of galectin-1 in EBV-positive lymphomas and the EBV-specific CTL immune response.
34. Juszczynski P, Ouyang J, Monti S, et al. The AP1-dependent secretion of galectin-1 by Reed Sternberg cells fosters immune privilege in classical Hodgkin lymphoma. Proc Natl Acad Sci U S A. 2007;104:13134-9.
35. Young RM, Hardy IR, Clarke RL, et al. Mouse models of non-Hodgkin lymphoma reveal Syk as an important therapeutic target. Blood. 2009;113:2508-16.
36. Hatton O, Phillips LK, Vaysberg M, Hurwich J, Krams SM, Martinez OM. Syk activation of phosphatidylinositol 3-kinase/Akt prevents HtrA2-dependent loss of X-linked inhibitor of apoptosis protein (XIAP) to promote survival of Epstein-Barr virus+ (EBV+) B cell lymphomas. J Biol Chem. 2011;286:37368-78. LMP-2 signaling through the Syk and the PI3K/Akt pathway in EBV-positive lymphomas.
37. Chen L, Monti S, Juszczynski P, et al. SYK-dependent tonic B-cell receptor signaling is a rational treatment target in diffuse large B-cell lymphoma. Blood. 2008;111:2230-7.
38. Gururajan M, Dasu T, Shahidain S, et al. Spleen tyrosine kinase (Syk), a novel target of curcumin, is required for B lymphoma growth. J Immunol. 2007;178:111-21.
39. Suljagic M, Longo PG, Bennardo S, et al. The Syk inhibitor fostamatinib disodium (R788) inhibits tumor growth in the Emu- TCL1 transgenic mouse model of CLL by blocking antigen-dependent B-cell receptor signaling. Blood. 2010;116:4894-905.
40. Friedberg JW, Sharman J, Sweetenham J, et al. Inhibition of Syk with fostamatinib disodium has significant clinical activity in non-Hodgkin lymphoma and chronic lymphocytic leukemia. Blood. 2010;115:2578-85.
41. Braselmann S, Taylor V, Zhao H, et al. R406, an orally available spleen tyrosine kinase inhibitor blocks fc receptor signaling and reduces immune complex-mediated inflammation. J Pharmacol Exp Ther. 2006;319:998-1008.
42. Caldwell RG, Brown RC, Longnecker R. Epstein-Barr virus LMP2A-induced B-cell survival in two unique classes of EmuLMP2A transgenic mice. J Virol. 2000;74:1101-13.
43. Bultema R, Longnecker R, Swanson-Mungerson M. Epstein-Barr virus LMP2A accelerates MYC-induced lymphomagenesis. Oncogene. 2009;28:1471-6.
44. Rovedo M, Longnecker R. Epstein-Barr virus latent membrane protein 2A preferentially signals through the Src family kinase Lyn. J Virol. 2008;82:8520-8.
45. Dargart JL, Fish K, Gordon LI, Longnecker R, Cen O. Dasatinib therapy results in decreased B cell proliferation, splenomegaly, and tumor growth in a murine model of lymphoma expressing Myc and Epstein-Barr virus LMP2A. Antiviral Res. 2012;95:49-56. Dasatinib inhibts LMP-2-mediated activation of the Lyn pathway and leads to regression of EBV(+) lymphomas in a murine model.
46. Dawson CW, Tramountanis G, Eliopoulos AG, Young LS. Epstein-Barr virus latent membrane protein 1 (LMP1) activates the phosphatidylinositol 3-kinase/Akt pathway to promote cell survival and induce actin filament remodeling. J Biol Chem. 2003;278:3694-704.
47. Lambert SL, Martinez OM. Latent membrane protein 1 of EBV activates phosphatidylinositol 3-kinase to induce production of IL-10. J Immunol. 2007;179:8225-34.
48. Hatton O, Lambert SL, Krams SM, Martinez OM. Src kinase and Syk activation initiate PI3K signaling by a chimeric latent membrane protein 1 in Epstein-Barr virus (EBV)+ B cell lymphomas. PLoS One. 2012;7:e42610. LMP-1 activates the P13K/Akt pathway through Syk activation.
49. Meckes DG, Jr., Menaker NF, Raab-Traub N. EBV LMP1 Modulates Lipid Raft Microdomains and the Vimentin Cytoskeleton for Signal Transduction and Transformation. J Virol 2012.
50. Kanemitsu N, Isobe Y, Masuda A, et al. Expression of Epstein-Barr virus-encoded proteins in extranodal NK/T-cell Lymphoma, nasal type (ENKL): differences in biologic and clinical behaviors of LMP1-positive and -negative ENKL. Clin Cancer Res. 2012;18:2164-72.
51. Or YY, Hui AB, To KF, Lam CN, Lo KW. PIK3CA mutations in nasopharyngeal carcinoma. Int J Cancer. 2006;118:1065-7.
52. Ma BB, Lui VW, Hui EP, et al. The activity of mTOR inhibitor RAD001 (everolimus) in nasopharyngeal carcinoma and cisplatin-resistant cell lines. Invest New Drugs. 2010;28:413-20.
53. Mei YP, Zhou JM, Wang Y, et al. Silencing of LMP1 induces cell cycle arrest and enhances chemosensitivity through inhibition of AKT signaling pathway in EBV-positive nasopharyngeal carcinoma cells. Cell Cycle. 2007;6:1379-85.
54. Ma BB, Lui VW, Hui CW, et al. Preclinical evaluation of the AKT inhibitor MK-2206 in nasopharyngeal carcinoma cell lines. Invest New Drugs 2012.
55. Green MR, Rodig S, Juszczynski P, et al. Constitutive AP-1 activity and EBV infection induce PD-L1 in Hodgkin lymphomas and posttransplant lymphoproliferative disorders: implications for targeted therapy. Clin Cancer Res. 2012;18:1611-8. EBV as a mechanism of PD-L1 induction in EBV-positive lymphomas.
56. Shirley CM, Chen J, Shamay M, et al. Bortezomib induction of C/EBPbeta mediates Epstein-Barr virus lytic activation in Burkitt lymphoma. Blood. 2011;117:6297-303. Bortezomib induces the unfolded protein response and CEBP-α-mediated lytic activation of EBV in Burkitt lymphoma.
57. Sides MD, Block GJ, Shan B, et al. Arsenic mediated disruption of promyelocytic leukemia protein nuclear bodies induces ganciclovir susceptibility in Epstein-Barr positive epithelial cells. Virology. 2011;416:86-97.
58. Sivachandran N, Wang X, Frappier L. Functions of the Epstein-Barr virus EBNA1 protein in viral reactivation and lytic infection. J Virol. 2012;86:6146-58.
59. Li R, Wang L, Liao G, et al. SUMO binding by the Epstein-Barr virus protein kinase BGLF4 is crucial for BGLF4 function. J Virol. 2012;86:5412-21. Role of SUMO binding of BGLF4 in the DNA damage response and EBV replication.
60. Hui KF, Chiang AK. Suberoylanilide hydroxamic acid induces viral lytic cycle in Epstein-Barr virus-positive epithelial malignancies and mediates enhanced cell death. Int J Cancer. 2010;126:2479-89.
61. Ghosh SK, Perrine SP, Williams RM, Faller DV. Histone deacetylase inhibitors are potent inducers of gene expression in latent EBV and sensitize lymphoma cells to nucleoside antiviral agents. Blood. 2012;119:1008-17. Lytic induction of EBV with histone deacetylase inhibitors.
62. Wildeman MA, Novalic Z, Verkuijlen SA, et al. Cytolytic virus activation therapy for epstein-barr virus-driven tumors. Clin Cancer Res. 2012;18:5061-70. Lytic induction of EBV with gemcitabine and valproic acid.
63. Jones K, Nourse J, Corbett G, Gandhi MK. Sodium valproate in combination with ganciclovir induces lysis of EBV-infected lymphoma cells without impairing EBV-specific T-cell immunity. Int J Lab Hematol. 2010;32:e169-74.
64. Perrine SP, Hermine O, Small T, et al. A phase 1/2 trial of arginine butyrate and ganciclovir in patients with Epstein-Barr virus-associated lymphoid malignancies. Blood. 2007;109:2571-8.
65. Jung EJ, Lee YM, Lee BL, Chang MS, Kim WH. Lytic induction and apoptosis of Epstein-Barr virus-associated gastric cancer cell line with epigenetic modifiers and ganciclovir. Cancer Lett. 2007;247:77-83.
66. Li Y, Zhang Y, Fu M, et al. Parthenolide induces apoptosis and lytic cytotoxicity in Epstein-Barr virus-positive Burkitt lymphoma. Mol Med Report. 2012;6:477-82. Lytic induction of EBV with parthenolide.
67. Hagemeier SR, Barlow EA, Meng Q, Kenney SC. The cellular ataxia telangiectasia-mutated (ATM) kinase promotes Epstein-Barr virus (EBV) lytic reactivation in response to multiple different types of lytic-inducing stimuli. J Virol 2012. Role of ATM kinase in EBV lytic activation.
68. Sokal EM, Hoppenbrouwers K, Vandermeulen C, et al. Recombinant gp350 vaccine for infectious mononucleosis: a phase 2, randomized, double-blind, placebo-controlled trial to evaluate the safety, immunogenicity, and efficacy of an Epstein-Barr virus vaccine in healthy young adults. J Infect Dis. 2007;196:1749-53.
69. Moutschen M, Leonard P, Sokal EM, et al. Phase I/II studies to evaluate safety and immunogenicity of a recombinant gp350 Epstein-Barr virus vaccine in healthy adults. Vaccine. 2007;25:4697-705.
70. Elliott SL, Suhrbier A, Miles JJ, et al. Phase I trial of a CD8+ T-cell peptide epitope-based vaccine for infectious mononucleosis. J Virol. 2008;82:1448-57.
71. Cohen JI, Fauci AS, Varmus H, Nabel GJ. Epstein-Barr virus: an important vaccine target for cancer prevention. Sci Transl Med 2011;3:107fs107. Overview of EBV vaccine development, clinical trials, and future directions.
72. Rees L, Tizard EJ, Morgan AJ, et al. A phase I trial of epstein-barr virus gp350 vaccine for children with chronic kidney disease awaiting transplantation. Transplantation. 2009;88:1025-9.