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Adoptive T-Cell Immunotherapy

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Epstein Barr Virus Volume 2

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 391))

Abstract

Epstein-Barr virus (EBV) is associated with a range of malignancies involving B cells, T cells, natural killer (NK) cells, epithelial cells, and smooth muscle. All of these are associated with the latent life cycles of EBV, but the pattern of latency-associated viral antigens expressed in tumor cells depends on the type of tumor. EBV-specific T cells (EBVSTs) have been explored as prophylaxis and therapy for EBV-associated malignancies for more than two decades. EBVSTs have been most successful as prophylaxis and therapy for post-transplant lymphoproliferative disease (PTLD) , which expresses the full array of latent EBV antigens (type 3 latency), in hematopoietic stem-cell transplant (HSCT) recipients. While less effective, clinical studies have also demonstrated their therapeutic potential for PTLD post-solid organ transplant and for EBV-associated malignancies such as Hodgkin’s lymphoma, non-Hodgkin’s lymphoma, and nasopharyngeal carcinoma (NPC) that express a limited array of latent EBV antigens (type 2 latency). Several approaches are actively being pursued to improve the antitumor activity of EBVSTs including activation and expansion of T cells specific for the EBV antigens expressed in type 2 latency, genetic approaches to render EBVSTs resistant to the immunosuppressive tumor environment, and combination approaches with other immune-modulating modalities. Given the recent advances and renewed interest in cell therapy, we hope that EBVSTs will become an integral part of our treatment armamentarium against EBV-positive malignancies in the near-future.

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References

  • Apcher S, Daskalogianni C, Manoury B et al (2010) Epstein Barr virus-encoded EBNA1 interference with MHC class I antigen presentation reveals a close correlation between mRNA translation initiation and antigen presentation. PLoS Pathog 6(10):e1001151

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Barker JN, Doubrovina E, Sauter C et al (2010) Successful treatment of EBV-associated posttransplantation lymphoma after cord blood transplantation using third-party EBV-specific cytotoxic T lymphocytes. Blood 116(23):5045–5049

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Bollard CM, Rossig C, Calonge MJ et al (2002) Adapting a transforming growth factor beta-related tumor protection strategy to enhance antitumor immunity. Blood 99(9):3179–3187

    Article  CAS  PubMed  Google Scholar 

  • Bollard CM, Aguilar L, Straathof KC et al (2004) Cytotoxic T lymphocyte therapy for Epstein-Barr virus+ Hodgkin’s disease. J Exp Med 200(12):1623–1633

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Bollard CM, Gottschalk S, Leen AM et al (2007) Complete responses of relapsed lymphoma following genetic modification of tumor-antigen presenting cells and T-lymphocyte transfer. Blood 110(8):2838–2845

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Bollard CM, Dotti G, Gottschalk S et al (2012) Administration of TGF-beta resistant tumor-specific CTL to patienst with EBV-associated HL and NHL. Mol Ther 20(Supplement 1):S22

    Google Scholar 

  • Bollard CM, Gottschalk S, Torrano V et al (2014) Sustained complete responses in patients with lymphoma receiving autologous cytotoxic T lymphocytes targeting Epstein-Barr virus latent membrane proteins. J Clin Oncol 32(8):798–808

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Bonini C, Brenner MK, Heslop HE et al (2011) Genetic modification of T cells. Biol Blood Marrow Transplant 17(1 Suppl):S15–S20

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Brahmer JR, Tykodi SS, Chow LQ et al (2012) Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med 366(26):2455–2465

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Brentjens RJ, Davila ML, Riviere I et al (2013) CD19-targeted T cells rapidly induce molecular remissions in adults with chemotherapy-refractory acute lymphoblastic leukemia. Sci Transl Med 5(177):177ra38

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Brewin J, Mancao C, Straathof K et al (2009) Generation of EBV-specific cytotoxic T cells that are resistant to calcineurin inhibitors for the treatment of posttransplantation lymphoproliferative disease. Blood 114(23):4792–4803

    Article  CAS  PubMed  Google Scholar 

  • Brooks L, Yao QY, Rickinson AB et al (1992) Epstein-Barr virus latent gene transcription in nasopharyngeal carcinoma cells: coexpression of EBNA1, LMP1, and LMP2 transcripts. J Virol 66(5):2689–2697

    PubMed Central  CAS  PubMed  Google Scholar 

  • Buettner M, Meyer B, Schreck S et al (2007) Expression of RANTES and MCP-1 in epithelial cells is regulated via LMP1 and CD40. Int J Cancer 121(12):2703–2710

    Article  CAS  PubMed  Google Scholar 

  • Cavazzana-Calvo M, Fischer A, Hacein-Bey-Abina S et al (2012) Gene therapy for primary immunodeficiencies: Part 1. Curr Opin Immunol 24(5):580–584

    Article  CAS  PubMed  Google Scholar 

  • Chan AT, Tao Q, Robertson KD et al (2004) Azacitidine induces demethylation of the Epstein-Barr virus genome in tumors. J Clin Oncol 22(8):1373–1381

    Article  CAS  PubMed  Google Scholar 

  • Chen L, Huang TG, Meseck M et al (2007) Rejection of metastatic 4T1 breast cancer by attenuation of Treg cells in combination with immune stimulation. Mol Ther 15(12):2194–2202

    Article  CAS  PubMed  Google Scholar 

  • Chia WK, Teo M, Wang WW et al (2014) Adoptive T-cell transfer and chemotherapy in the first-line treatment of metastatic and/or locally recurrent nasopharyngeal carcinoma. Mol Ther 22(1):132–139

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Chiang AK, Tao Q, Srivastava G et al (1996) Nasal NK- and T-cell lymphomas share the same type of Epstein-Barr virus latency as nasopharyngeal carcinoma and Hodgkin’s disease. Int J Cancer 68(3):285–290

    Article  CAS  PubMed  Google Scholar 

  • Chinnasamy D, Yu Z, Kerkar SP et al (2012) Local delivery of interleukin-12 using T cells targeting VEGF receptor-2 eradicates multiple vascularized tumors in mice. Clin Cancer Res 18(6):1672–1683

    Article  CAS  PubMed  Google Scholar 

  • Chua D, Huang J, Zheng B et al (2001) Adoptive transfer of autologous Epstein-Barr virus-specific cytotoxic T cells for nasopharyngeal carcinoma. Int J Cancer 94(1):73–80

    Article  CAS  PubMed  Google Scholar 

  • Cobbold M, Khan N, Pourgheysari B et al (2005) Adoptive transfer of cytomegalovirus-specific CTL to stem cell transplant patients after selection by HLA-peptide tetramers. J Exp Med 202(3):379–386

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Cobbold M, De La Pena H, Norris A et al (2013) MHC class I-associated phosphopeptides are the targets of memory-like immunity in leukemia. Sci Transl Med 5(203):203ra125

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Comoli P, Locatelli F, Gerna G et al (1997) Autologous EBV-specific cytotoxic T cells to treat EBV-associated post-transplant lymphoproliferative disease (PTLD). Blood 90(10):249a

    Google Scholar 

  • Comoli P, Labirio M, Basso S et al (2002) Infusion of autologous Epstein-Barr virus (EBV)-specific cytotoxic T cells for prevention of EBV-related lymphoproliferative disorder in solid organ transplant recipients with evidence of active virus replication. Blood 99(7):2592–2598

    Article  CAS  PubMed  Google Scholar 

  • Comoli P, Pedrazzoli P, Maccario R et al (2005) Cell therapy of stage IV nasopharyngeal carcinoma with autologous Epstein-Barr virus-targeted cytotoxic T lymphocytes. J Clin Oncol 23(35):8942–8949

    Article  CAS  PubMed  Google Scholar 

  • Conlon KC, Lugli E, Welles HC et al (2014) Redistribution, hyperproliferation, activation of natural killer cells and CD8 T cells, and cytokine production during first-in-human clinical trial of recombinant human interleukin-15 in patients with cancer. J Clin Oncol 33:74–84

    Article  PubMed  CAS  Google Scholar 

  • Cruz CR, Micklethwaite KP, Savoldo B et al (2013) Infusion of donor-derived CD19-redirected virus-specific T cells for B-cell malignancies relapsed after allogeneic stem cell transplant: a phase 1 study. Blood 122(17):2965–2973

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Cruz-Merino L, Lejeune M, Nogales FE et al (2012) Role of immune escape mechanisms in Hodgkin’s lymphoma development and progression: a whole new world with therapeutic implications. Clin Dev Immunol 2012:756353

    PubMed Central  PubMed  Google Scholar 

  • De Angelis B, Dotti G, Quintarelli C et al (2009) Generation of virus-specific cytotoxic T lymphocytes (Ctls) resistant to the immunosuppressive drug tacrolimus (Fk506). Biol Blood Marrow Transplant 15(2):377

    Article  Google Scholar 

  • De AB, Dotti G, Quintarelli C et al (2009) Generation of Epstein-Barr virus-specific cytotoxic T lymphocytes resistant to the immunosuppressive drug tacrolimus (FK506). Blood 114(23):4784–4791

    Article  CAS  Google Scholar 

  • Decaussin G, Sbih-Lammali F, de Turenne-Tessier M et al (2000) Expression of BARF1 gene encoded by Epstein-Barr virus in nasopharyngeal carcinoma biopsies. Cancer Res 60(19):5584–5588

    CAS  PubMed  Google Scholar 

  • Di Stasi A, De Angelis B, Rooney CM et al (2009) T lymphocytes coexpressing CCR4 and a chimeric antigen receptor targeting CD30 have improved homing and antitumor activity in a Hodgkin tumor model. Blood 113(25):6392–6402

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Di Stasi A, Tey SK, Dotti G et al (2011) Inducible apoptosis as a safety switch for adoptive cell therapy. N Engl J Med 365(18):1673–1683

    Article  PubMed Central  PubMed  Google Scholar 

  • Dotti G, Savoldo B, Pule M et al (2005) Human cytotoxic T lymphocytes with reduced sensitivity to Fas-induced apoptosis. Blood 105(12):4677–4684

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Dotti G, Gottschalk S, Savoldo B et al (2014) Design and development of therapies using chimeric antigen receptor-expressing T cells. Immunol Rev 257(1):107–126

    Article  CAS  PubMed  Google Scholar 

  • Doubrovina E, Oflaz-Sozmen B, Prockop SE et al (2012) Adoptive immunotherapy with unselected or EBV-specific T cells for biopsy-proven EBV+ lymphomas after allogeneic hematopoietic cell transplantation. Blood 119(11):2644–2656

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Dudley ME, Yang JC, Sherry R et al (2008) Adoptive cell therapy for patients with metastatic melanoma: evaluation of intensive myeloablative chemoradiation preparative regimens. J Clin Oncol 26(32):5233–5239

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Feng WH, Kenney SC (2006) Valproic acid enhances the efficacy of chemotherapy in EBV-positive tumors by increasing lytic viral gene expression. Cancer Res 66(17):8762–8769

    Article  CAS  PubMed  Google Scholar 

  • Feng WH, Hong G, Delecluse HJ et al (2004) Lytic induction therapy for Epstein-Barr virus-positive B-cell lymphomas. J Virol 78(4):1893–1902

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Feuchtinger T, Lang P, Hamprecht K et al (2004) Isolation and expansion of human adenovirus-specific CD4+ and CD8+ T cells according to IFN-gamma secretion for adjuvant immunotherapy. Exp Hematol 32(3):282–289

    Article  CAS  PubMed  Google Scholar 

  • Feuchtinger T, Opherk K, Bethge WA et al (2010) Adoptive transfer of pp65-specific T cells for the treatment of chemorefractory cytomegalovirus disease or reactivation after haploidentical and matched unrelated stem cell transplantation. Blood 116(20):4360–4367

    Article  CAS  PubMed  Google Scholar 

  • Fiorini S, Ooka T (2008) Secretion of Epstein-Barr virus-encoded BARF1 oncoprotein from latently infected B cells. Virol J 5:70

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Fogg MH, Wirth LJ, Posner M et al (2009) Decreased EBNA-1-specific CD8+ T cells in patients with Epstein-Barr virus-associated nasopharyngeal carcinoma. Proc Natl Acad Sci USA 106(9):3318–3323

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Fogg M, Murphy JR, Lorch J et al (2013) Therapeutic targeting of regulatory T cells enhances tumor-specific CD8+ T cell responses in Epstein-Barr virus associated nasopharyngeal carcinoma. Virology 441(2):107–113

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Foster AE, Dotti G, Lu A et al (2008) Antitumor activity of EBV-specific T lymphocytes transduced with a dominant negative TGF-beta receptor. J Immunother 31(5):500–505

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Gahn B, Siller-Lopez F, Pirooz AD et al (2001) Adenoviral gene transfer into dendritic cells efficiently amplifies the immune response to the LMP2A-antigen: a potential treatment strategy for Epstein-Barr virus-positive Hodgkin’s lymphoma. Int J Cancer 93(5):706–713

    Article  CAS  PubMed  Google Scholar 

  • Gerdemann U, Christin AS, Vera JF et al (2009) Nucleofection of DCs to generate Multivirus-specific T cells for prevention or treatment of viral infections in the immunocompromised host. Mol Ther 17(9):1616–1625

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Gerdemann U, Keirnan JM, Katari UL et al (2012) Rapidly generated multivirus-specific cytotoxic T lymphocytes for the prophylaxis and treatment of viral infections. Mol Ther 20(8):1622–1632

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Gerdemann U, Katari UL, Papadopoulou A et al (2013) Safety and clinical efficacy of rapidly-generated trivirus-directed T cells as treatment for adenovirus, EBV, and CMV infections after allogeneic hematopoietic stem cell transplant. Mol Ther 21(11):2113–2121

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Gilligan KJ, Rajadurai P, Lin JC et al (1991) Expression of the Epstein-Barr virus BamHI a fragment in nasopharyngeal carcinoma: evidence for a viral protein expressed in vivo. J Virol 65(11):6252–6259

    PubMed Central  CAS  PubMed  Google Scholar 

  • Gottschalk S, Edwards OL, Sili U et al (2003) Generating CTL against the subdominant Epstein-Barr virus LMP1 antigen for the adoptive immunotherapy of EBV-associated malignancies. Blood 101(5):1905–1912

    Article  CAS  PubMed  Google Scholar 

  • Grupp SA, Kalos M, Barrett D et al (2013) Chimeric antigen receptor-modified T cells for acute lymphoid leukemia. N Engl J Med 368(16):1509–1518

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Hacein-Bey-Abina S, Hauer J, Lim A et al (2010) Efficacy of gene therapy for X-linked severe combined immunodeficiency. N Engl J Med 363(4):355–364

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Haque T, Amlot PL, Helling N et al (1998) Reconstitution of EBV-specific T cell immunity in solid organ transplant recipients. J Immunol 160(12):6204–6209

    CAS  PubMed  Google Scholar 

  • Haque T, Wilkie GM, Taylor C et al (2002) Treatment of Epstein-Barr-virus-positive post-transplantation lymphoproliferative disease with partly HLA-matched allogeneic cytotoxic T cells. Lancet 360(9331):436–442

    Article  PubMed  Google Scholar 

  • Haque T, Wilkie GM, Jones MM et al (2007) Allogeneic cytotoxic T-cell therapy for EBV-positive posttransplantation lymphoproliferative disease: results of a phase 2 multicenter clinical trial. Blood 110(4):1123–1131

    Article  CAS  PubMed  Google Scholar 

  • Herbst H, Dallenbach F, Hummel M et al (1991) Epstein-Barr virus latent membrane protein expression in Hodgkin and Reed-Sternberg cells. Proc Natl Acad Sci USA 88(11):4766–4770

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Heslop HE, Ng CYC, Li C et al (1996) Long-term restoration of immunity against Epstein-Barr virus infection by adoptive transfer of gene-modified virus-specific T lymphocytes. Nat Med 2:551–555

    Article  CAS  PubMed  Google Scholar 

  • Heslop HE, Slobod KS, Pule MA et al (2010) Long-term outcome of EBV-specific T-cell infusions to prevent or treat EBV-related lymphoproliferative disease in transplant recipients. Blood 115(5):925–935

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Hodi FS, O’Day SJ, McDermott DF et al (2010) Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 363(8):711–723

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Huye LE, Nakazawa Y, Patel MP et al (2011) Combining mTor inhibitors with rapamycin-resistant T cells: a two-pronged approach to tumor elimination. Mol Ther 19(12):2239–2248

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Icheva V, Kayser S, Wolff D et al (2013) 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 31(1):39–48

    Article  CAS  PubMed  Google Scholar 

  • John LB, Devaud C, Duong CP et al (2013) Anti-PD-1 antibody therapy potently enhances the eradication of established tumors by gene-modified T cells. Clin Cancer Res 19(20):5636–5646

    Article  CAS  PubMed  Google Scholar 

  • Jonnalagadda M, Brown CE, Chang WC et al (2013) Engineering human T cells for resistance to methotrexate and mycophenolate mofetil as an in vivo cell selection strategy. PLoS ONE 8(6):e65519

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Kalos M, Levine BL, Porter DL et al (2011) T cells with chimeric antigen receptors have potent antitumor effects and can establish memory in patients with advanced leukemia. Sci Transl Med 3(95):95ra73

    Google Scholar 

  • Kern F, Faulhaber N, Frommel C et al (2000) Analysis of CD8 T cell reactivity to cytomegalovirus using protein-spanning pools of overlapping pentadecapeptides. Eur J Immunol 30(6):1676–1682

    Article  CAS  PubMed  Google Scholar 

  • Khanna R, Bell S, Sherritt M et al (1999) Activation and adoptive transfer of Epstein-Barr virus-specific cytotoxic T cells in solid organ transplant patients with posttransplant lymphoproliferative disease. Proc Natl Acad Sci USA 96(18):10391–10396

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Lee SP, Brooks JM, Al-Jarrah H et al (2004) CD8 T cell recognition of endogenously expressed epstein-barr virus nuclear antigen 1. J Exp Med 199(10):1409–1420

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Leen A, Meij P, Redchenko I et al (2001) Differential immunogenicity of Epstein-Barr virus latent-cycle proteins for human CD4(+) T-helper 1 responses. J Virol 75(18):8649–8659

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Leen AM, Myers GD, Sili U et al (2006) Monoculture-derived T lymphocytes specific for multiple viruses expand and produce clinically relevant effects in immunocompromised individuals. Nat Med 12(10):1160–1166

    Article  CAS  PubMed  Google Scholar 

  • Leen AM, Rooney CM, Foster AE (2007) Improving T cell therapy for cancer. Annu Rev Immunol 25:243–265

    Article  CAS  PubMed  Google Scholar 

  • Leen AM, Christin A, Myers GD et al (2009) Cytotoxic T lymphocyte therapy with donor T cells prevents and treats adenovirus and Epstein-Barr virus infections after haploidentical and matched unrelated stem cell transplantation. Blood 114(19):4283–4292

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Leen AM, Bollard CM, Mendizabal AM et al (2013) Multicenter study of banked third-party virus-specific T cells to treat severe viral infections after hematopoietic stem cell transplantation. Blood 121(26):5113–5123

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Leen AM, Sukumaran S, Watanabe N et al (2014) Reversal of tumor immune inhibition using a chimeric cytokine receptor. Mol Ther 22(6):1211–1220

    PubMed Central  CAS  PubMed  Google Scholar 

  • Levitskaya J, Coram M, Levitsky V et al (1995) Inhibition of antigen processing by the internal repeat region of the Epstein-Barr virus nuclear antigen-1. Nature 375(6533):685–688

    Article  CAS  PubMed  Google Scholar 

  • Levitskaya J, Sharipo A, Leonchiks A et al (1997) Inhibition of ubiquitin/proteasome-dependent protein degradation by the Gly-Ala repeat domain of the Epstein-Barr virus nuclear antigen 1. Proc Natl Acad Sci 94(23):12616–12621

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Linnerbauer S, Behrends U, Adhikary D et al (2014) Virus and autoantigen-specific CD4+ T cells are key effectors in a SCID mouse model of EBV-associated post-transplant lymphoproliferative disorders. PLoS Pathog 10(5):e1004068

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Louis CU, Straathof K, Bollard CM et al (2010) Adoptive transfer of EBV-specific T cells results in sustained clinical responses in patients with locoregional nasopharyngeal carcinoma. J Immunother 33(9):983–990

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Louis CU, Savoldo B, Dotti G et al (2011) Antitumor activity and long-term fate of chimeric antigen receptor-positive T cells in patients with neuroblastoma. Blood 118(23):6050–6056

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Lucas KG, Salzman D, Garcia A et al (2004) Adoptive immunotherapy with allogeneic Epstein-Barr virus (EBV)-specific cytotoxic T-lymphocytes for recurrent, EBV-positive Hodgkin disease. Cancer 100(9):1892–1901

    Article  PubMed  Google Scholar 

  • Moosmann A, Bigalke I, Tischer J et al (2010) Effective and long-term control of EBV PTLD after transfer of peptide-selected T cells. Blood 115(14):2960–2970

    Article  CAS  PubMed  Google Scholar 

  • Moskwa M, Ribrag V, Michot J-M et al (2014) PD-1 blockade with the monoclonal antibody pembrolizumab (MK-3475) in patients with classical Hodgkin lymphoma after brentuximab vedotin failure: preliminary results from a phase 1b study. Blood 24(21):290

    Google Scholar 

  • Mrizak D, Martin N, Barjon C et al (2015) Effect of nasopharyngeal carcinoma-derived exosomes on human regulatory T cells. J Natl Cancer Inst 107(1):363

    Google Scholar 

  • Munz C (2004) Epstein-barr virus nuclear antigen 1: from immunologically invisible to a promising T cell target. J Exp Med 199(10):1301–1304

    Article  PubMed Central  PubMed  Google Scholar 

  • Munz C, Bickham KL, Subklewe M et al (2000) Human CD4(+) T lymphocytes consistently respond to the latent Epstein-Barr virus nuclear antigen EBNA1. J Exp Med 191(10):1649–1660

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Ngo MC, Ando J, Leen AM et al (2014) Complementation of antigen-presenting cells to generate T lymphocytes with broad target specificity. J Immunother 37(4):193–203

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Nikiforow S, Bottomly K, Miller G (2001) CD4+ T-cell effectors inhibit Epstein-Barr virus-induced B-cell proliferation. J Virol 75(8):3740–3752

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Pallesen G, Hamilton-Dutoit SJ, Rowe M et al (1991) Expression of Epstein-Barr virus latent gene products in tumour cells of Hodgkin’s disease. Lancet 337:320–322

    Article  CAS  PubMed  Google Scholar 

  • Paludan C, Bickham K, Nikiforow S et al (2002) Epstein-Barr nuclear antigen 1-specific CD4(+) Th1 cells kill Burkitt’s lymphoma cells. J Immunol 169(3):1593–1603

    Article  CAS  PubMed  Google Scholar 

  • Papadopoulou A, Gerdemann U, Katari UL et al (2014) Activity of broad-spectrum T cells as treatment for AdV, EBV, CMV, BKV, and HHV6 infections after HSCT. Sci Transl Med 6(242):242ra83

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Peggs KS, Thomson K, Samuel E et al (2011) Directly selected cytomegalovirus-reactive donor T cells confer rapid and safe systemic reconstitution of virus-specific immunity following stem cell transplantation. Clin Infect Dis 52(1):49–57

    Article  CAS  PubMed  Google Scholar 

  • Pegram HJ, Lee JC, Hayman EG et al (2012) Tumor-targeted T cells modified to secrete IL-12 eradicate systemic tumors without need for prior conditioning. Blood 119(18):4133–4141

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Perna SK, De AB, Pagliara D et al (2013) Interleukin 15 provides relief to CTLs from regulatory T cell-mediated inhibition: implications for adoptive T cell-based therapies for lymphoma. Clin Cancer Res 19(1):106–117

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Perna SK, Pagliara D, Mahendravada A et al (2014) Interleukin-7 mediates selective expansion of tumor-redirected cytotoxic T lymphocytes (CTLs) without enhancement of regulatory T-cell inhibition. Clin Cancer Res 20(1):131–139

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Perrine SP, Hermine O, Small T et al (2007) A phase 1/2 trial of arginine butyrate and ganciclovir in patients with Epstein-Barr virus-associated lymphoid malignancies. Blood 109(6):2571–2578

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Poppema S (2005) Immunobiology and pathophysiology of hodgkin lymphomas. Hematol Am Soc Hematol Educ Program 2005:231–238

    Article  Google Scholar 

  • Porter DL, Roth MS, McGarigle C et al (1994) Induction of graft-versus-host disease as immunotherapy for relapsed chronic myeloid leukemia. N Engl J Med 330(2):100–106

    Article  CAS  PubMed  Google Scholar 

  • Porter DL, Levine BL, Kalos M et al (2011) Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia. N Engl J Med 365(8):725–733

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Pudney VA, Leese AM, Rickinson AB et al (2005) CD8+ immunodominance among Epstein-Barr virus lytic cycle antigens directly reflects the efficiency of antigen presentation in lytically infected cells. J Exp Med 201(3):349–360

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Pule MA, Savoldo B, Myers GD et al (2008) Virus-specific T cells engineered to coexpress tumor-specific receptors: persistence and antitumor activity in individuals with neuroblastoma. Nat Med 14(11):1264–1270

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Rabinovich GA, Gabrilovich D, Sotomayor EM (2007) Immunosuppressive strategies that are mediated by tumor cells. Annu Rev Immunol 25:267–296

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Ricciardelli I, Blundell MP, Brewin J et al (2014) Towards gene therapy for EBV-associated posttransplant lymphoma with genetically modified EBV-specific cytotoxic T cells. Blood 124(16):2514–2522

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Rooney CM, Smith CA, Ng C et al (1995) Use of gene-modified virus-specific T lymphocytes to control Epstein-Barr virus-related lymphoproliferation. Lancet 345:9–13

    Article  CAS  PubMed  Google Scholar 

  • Rooney CM, Smith CA, Ng CYC et al (1998) Infusion of cytotoxic T cells for the prevention and treatment of Epstein-Barr virus-induced lymphoma in allogeneic transplant recipients. Blood 92(5):1549–1555

    CAS  PubMed  Google Scholar 

  • Rosenberg SA, Dudley ME (2009) Adoptive cell therapy for the treatment of patients with metastatic melanoma. Curr Opin Immunol 21(2):233–240

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Rosenstein M, Ettinghausen SE, Rosenberg SA (1986) Extravasation of intravascular fluid mediated by the systemic administration of recombinant interleukin 2. J Immunol 137(5):1735–1742

    CAS  PubMed  Google Scholar 

  • Rowe M, Rowe DT, Gregory CD et al (1987) Differences in B cell growth phenotype reflect novel patterns of Epstein-Barr virus latent gene expression in Burkitt’s lymphoma cells. EMBO J 6:2743–2751

    PubMed Central  CAS  PubMed  Google Scholar 

  • Savoldo B, Goss J, Liu Z et al (2001) Generation of autologous Epstein Barr virus (EBV)-specific cytotoxic T cells (CTL) for adoptive immunotherapy in solid organ transplant recipients. Transplantation 72(6):1078–1086

    Article  CAS  PubMed  Google Scholar 

  • Savoldo B, Goss JA, Hammer MM et al (2006) Treatment of solid organ transplant recipients with autologous Epstein Barr virus-specific cytotoxic T lymphocytes (CTLs). Blood 108(9):2942–2949

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Savoldo B, Rooney CM, Di Stasi A et al (2007) Epstein Barr virus specific cytotoxic T lymphocytes expressing the anti-CD30zeta artificial chimeric T-cell receptor for immunotherapy of Hodgkin disease. Blood 110(7):2620–2630

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Secondino S, Zecca M, Licitra L et al (2012) T-cell therapy for EBV-associated nasopharyngeal carcinoma: preparative lymphodepleting chemotherapy does not improve clinical results. Ann Oncol 23(2):435–441

    Article  CAS  PubMed  Google Scholar 

  • Seto E, Yang L, Middeldorp J et al (2005) Epstein-Barr virus (EBV)-encoded BARF1 gene is expressed in nasopharyngeal carcinoma and EBV-associated gastric carcinoma tissues in the absence of lytic gene expression. J Med Virol 76(1):82–88

    Article  CAS  PubMed  Google Scholar 

  • Shaffer DR, Savoldo B, Yi Z et al (2011) T cells redirected against CD70 for the immunotherapy of CD70-positive malignancies. Blood 117(16):4304–4314

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Sherritt MA, Bharadwaj M, Burrows JM et al (2003) Reconstitution of the latent T-lymphocyte response to Epstein-Barr virus is coincident with long-term recovery from posttransplant lymphoma after adoptive immunotherapy. Transplantation 75(9):1556–1560

    Article  PubMed  Google Scholar 

  • Shirley CM, Chen J, Shamay M et al (2011) Bortezomib induction of C/EBPbeta mediates Epstein-Barr virus lytic activation in Burkitt lymphoma. Blood 117(23):6297–6303

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Smith C, Tsang J, Beagley L et al (2012) Effective treatment of metastatic forms of Epstein-Barr virus-associated nasopharyngeal carcinoma with a novel adenovirus-based adoptive immunotherapy. Cancer Res 72(5):1116–1125

    Article  CAS  PubMed  Google Scholar 

  • Song XT, Turnis M, Zhou X et al (2010) A Th1-inducing adenoviral vaccine for boosting adoptively transferred T cells. Mol Ther 19(1):211–217

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Sportes C, Hakim FT, Memon SA et al (2008) Administration of rhIL-7 in humans increases in vivo TCR repertoire diversity by preferential expansion of naive T cell subsets. J Exp Med 205(7):1701–1714

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Steigerwald-Mullen PM, Klein G, Kurilla MG et al (1995) Inhibition of antigen processing by the internal repeat region of the Epstein-Barr virus nuclear antigen-1. Nature 375(6533):685–688

    Article  PubMed  Google Scholar 

  • Steven NM, Annels NE, Kumar A et al (1997) Immediate early and early lytic cycle proteins are frequent targets of the Epstein-Barr virus-induced cytotoxic T cell response. J Exp Med 185(9):1605–1617

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Straathof KC, Bollard CM, Popat U et al (2005a) Treatment of nasopharyngeal carcinoma with Epstein-Barr virus-specific T lymphocytes. Blood 105:1898–1904

    Article  CAS  PubMed  Google Scholar 

  • Straathof KC, Pule MA, Yotnda P et al (2005b) An inducible caspase 9 safety switch for T-cell therapy. Blood 105(11):4247–4254

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Suhoski MM, Golovina TN, Aqui NA et al (2007) Engineering artificial antigen-presenting cells to express a diverse array of co-stimulatory molecules. Mol Ther 15(5):981–988

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Tellam JT, Lekieffre L, Zhong J et al (2012) Messenger RNA sequence rather than protein sequence determines the level of self-synthesis and antigen presentation of the EBV-encoded antigen, EBNA1. PLoS Pathog 8(12):e1003112

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Topalian SL, Hodi FS, Brahmer JR et al (2012) Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med 366(26):2443–2454

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Uhlin M, Gertow J, Uzunel M et al (2012) Rapid salvage treatment with virus-specific T cells for therapy-resistant disease. Clin Infect Dis 55(8):1064–1073

    Article  CAS  PubMed  Google Scholar 

  • Vera JF, Hoyos V, Savoldo B et al (2009) Genetic manipulation of tumor-specific cytotoxic T lymphocytes to restore responsiveness to IL-7. Mol Ther 17(5):880–888

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Vickers MA, Wilkie GM, Robinson N et al (2014) Establishment and operation of a good manufacturing practice-compliant allogeneic Epstein-Barr virus (EBV)-specific cytotoxic cell bank for the treatment of EBV-associated lymphoproliferative disease. Br J Haematol 167(3):402–410

    Article  PubMed Central  PubMed  Google Scholar 

  • Vogler I, Newrzela S, Hartmann S et al (2010) An improved bicistronic CD20/tCD34 vector for efficient purification and in vivo depletion of gene-modified T cells for adoptive immunotherapy. Mol Ther 18(7):1330–1338

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Voo KS, Fu T, Wang HY et al (2004) Evidence for the presentation of major histocompatibility complex class I-restricted Epstein-Barr virus nuclear antigen 1 peptides to CD8+ T lymphocytes. J Exp Med 199(4):459–470

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Wagner HJ, Bollard CM, Vigouroux S et al (2004) A strategy for treatment of Epstein-Barr virus-positive Hodgkin’s disease by targeting interleukin 12 to the tumor environment using tumor antigen-specific T cells. Cancer Gene Ther 11(2):81–91

    Article  CAS  PubMed  Google Scholar 

  • Wallace LE, Rickinson AB, Rowe M et al (1982) Stimulation of human lymphocytes with irradiated cells of the autologous Epstein-Barr virus-transformed cell line. I. Virus-specific and nonspecific components of the cytotoxic response. Cell Immunol 67(1):129–140

    Article  CAS  PubMed  Google Scholar 

  • Wang X, Chang WC, Wong CW et al (2011) A transgene-encoded cell surface polypeptide for selection, in vivo tracking, and ablation of engineered cells. Blood 118(5):1255–1263

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Watanabe N, Anurathapan U, Brenner M et al (2013) Transgenic expression of a novel immunosuppressive signal converter on T Cells. Mol Ther 22(S1):S153

    Google Scholar 

  • Wildeman MA, Novalic Z, Verkuijlen SA et al (2012) Cytolytic virus activation therapy for epstein-barr virus-driven tumors. Clin Cancer Res 18(18):5061–5070

    Article  CAS  PubMed  Google Scholar 

  • Wilkie S, Burbridge SE, Chiapero-Stanke L et al (2010) Selective expansion of chimeric antigen receptor-targeted T-cells with potent effector function using interleukin-4. J Biol Chem 285(33):25538–25544

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Xue SA, Labrecque LG, Lu QL et al (2002) Promiscuous expression of Epstein-Barr virus genes in Burkitt’s lymphoma from the central African country Malawi. Int J Cancer 99(5):635–643

    Article  CAS  PubMed  Google Scholar 

  • Yang L, Pang Y, Moses HL (2010) TGF-beta and immune cells: an important regulatory axis in the tumor microenvironment and progression. Trends Immunol 31(6):220–227

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Yin Y, Manoury B, Fahraeus R (2003) Self-inhibition of synthesis and antigen presentation by Epstein-Barr virus-encoded EBNA1. Science 301(5638):1371–1374

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We are grateful for the long-term support from the NIH (NCI, NHLBI), The Department of Defense, and The Leukemia and Lymphoma Society. We are also grateful to the foundations that have supported our research focused on EBV-associated malignancies including Alex’s Lemonade Stand Foundation, and the V Foundation. We thank the supporting faculty and staff of the Stem Cell Transplant Unit, Clinical Research Unit, and Cell Processing Laboratory at Texas Children’s Hospital and Houston Methodist Hospital. We also thank the patients who participated in our studies, and the parents who entrusted the care of their children to us.

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  1. Center for Cell and Gene Therapy, Texas Children’s Hospital, Houston Methodist Hospital, Baylor College of Medicine, 1102 Bates Street, Suite 1770, Houston, TX, 77030, USA

    Stephen Gottschalk & Cliona M. Rooney

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  1. Stephen Gottschalk
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  2. Cliona M. Rooney
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Correspondence to Stephen Gottschalk or Cliona M. Rooney .

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  1. Institute of Experimental Immunology, University of Zürich, Zürich, Switzerland

    Christian Münz

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Gottschalk, S., Rooney, C.M. (2015). Adoptive T-Cell Immunotherapy. In: Münz, C. (eds) Epstein Barr Virus Volume 2. Current Topics in Microbiology and Immunology, vol 391. Springer, Cham. https://doi.org/10.1007/978-3-319-22834-1_15

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