{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T22:07:47Z","timestamp":1789164467803,"version":"build-2803163510"},"reference-count":64,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2019,5,24]],"date-time":"2019-05-24T00:00:00Z","timestamp":1558656000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Infectious diseases are linked to 15%\u201320% of cancers worldwide. Among them, Epstein\u2013Barr virus (EBV) is an oncogenic herpesvirus that chronically infects over 90% of the adult population, with over 200,000 cases of cancer and 150,000 cancer-related deaths attributed to it yearly. Acute EBV infection can present as infectious mononucleosis, and lead to the future onset of multiple cancers, including Burkitt lymphoma, Hodgkin lymphoma, nasopharyngeal carcinoma, and gastric carcinoma. Many of these cancers express latent viral genes, including Epstein\u2013Barr virus nuclear antigen 1 (EBNA1) and latent membrane proteins 1 and 2 (LMP1 and LMP2). Previous attempts to create potent immunogens against EBV have been reported but generated mixed success. We designed novel Synthetic Consensus (SynCon) DNA vaccines against EBNA1, LMP1 and LMP2 to improve on the immune potency targeting important antigens expressed in latently infected cells. These EBV tumor antigens are hypothesized to be useful targets for potential immunotherapy of EBV-driven cancers. We optimized the genetic sequences for these three antigens, studied them for expression, and examined their immune profiles in vivo. We observed that these immunogens generated unique profiles based on which antigen was delivered as the vaccine target. EBNA1vax and LMP2Avax generated the most robust T cell immunity. Interestingly, LMP1vax was a very weak immunogen, generating very low levels of CD8 T cell immunity both as a standalone vaccine and as part of a trivalent vaccine cocktail. LMP2Avax was able to drive immunity that impacted EBV-antigen-positive tumor growth. These studies suggest that engineered EBV latent protein vaccines deserve additional study as potential agents for immunotherapy of EBV-driven cancers.<\/jats:p>","DOI":"10.3390\/vaccines7020044","type":"journal-article","created":{"date-parts":[[2019,5,24]],"date-time":"2019-05-24T11:20:46Z","timestamp":1558696846000},"page":"44","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Novel Synthetic DNA Immunogens Targeting Latent Expressed Antigens of Epstein\u2013Barr Virus Elicit Potent Cellular Responses and Inhibit Tumor Growth"],"prefix":"10.3390","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7834-2946","authenticated-orcid":false,"given":"Krzysztof","family":"Wojtak","sequence":"first","affiliation":[{"name":"Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA 19104, USA"},{"name":"Cell and Molecular Biology Graduate Program, The University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfredo","family":"Perales-Puchalt","sequence":"additional","affiliation":[{"name":"Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David B.","family":"Weiner","sequence":"additional","affiliation":[{"name":"Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,5,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1286","DOI":"10.1093\/infdis\/jit321","article-title":"Age-Specific Prevalence of Epstein-Barr Virus Infection Among Individuals Aged 6-19 Years in the United States and Factors Affecting Its Acquisition","volume":"208","author":"Balfour","year":"2013","journal-title":"J. Infect. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.jcv.2018.03.001","article-title":"Primary Epstein-Barr virus infection","volume":"102","author":"Dunmire","year":"2018","journal-title":"J. Clin. Virol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"4084","DOI":"10.1128\/jvi.64.9.4084-4092.1990","article-title":"Epstein-Barr virus types 1 and 2 differ in their EBNA-3A, EBNA-3B, and EBNA-3C genes","volume":"64","author":"Sample","year":"1990","journal-title":"J. Virol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1007\/s12275-018-8039-x","article-title":"Phylogenetic comparison of Epstein-Barr virus genomes","volume":"56","author":"Choi","year":"2018","journal-title":"J. Microbiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1097\/00007611-198708000-00003","article-title":"Epstein-Barr Virus: The Spectrum of Its Manifestations in Human Beings","volume":"80","author":"Purtilo","year":"1987","journal-title":"South. Med. J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1016\/S0140-6736(64)91524-7","article-title":"Virus Particles in Cultured Lymphoblasts from Burkitt\u2019s Lymphoma","volume":"1","author":"Epstein","year":"1964","journal-title":"Lancet"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.1056\/NEJMoa023141","article-title":"Characteristics of Hodgkin\u2019s lymphoma after infectious mononucleosis","volume":"349","author":"Hjalgrim","year":"2003","journal-title":"N. Engl. J. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1038\/2281056a0","article-title":"EBV DNA in biopsies of Burkitt tumours and anaplastic carcinomas of the nasopharynx","volume":"228","author":"Klein","year":"1970","journal-title":"Nature"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2461","DOI":"10.1056\/NEJMoa032260","article-title":"Quantification of plasma Epstein-Barr virus DNA in patients with advanced nasopharyngeal carcinoma","volume":"350","author":"Lin","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1053\/j.gastro.2009.05.001","article-title":"Meta-analysis shows that prevalence of Epstein-Barr virus-positive gastric cancer differs based on sex and anatomic location","volume":"137","author":"Murphy","year":"2009","journal-title":"Gastroenterology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/S1474-4422(14)70267-4","article-title":"Environmental risk factors and multiple sclerosis: An umbrella review of systematic reviews and meta-analyses","volume":"14","author":"Belbasis","year":"2015","journal-title":"Lancet Neurol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1007\/s10238-018-0535-0","article-title":"The risk of systemic lupus erythematosus associated with Epstein-Barr virus infection: A systematic review and meta-analysis","volume":"19","author":"Li","year":"2019","journal-title":"Clin. Exp. Med."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Draborg, A.H., Duus, K., and Houen, G. (2013). Epstein-Barr Virus in Systemic Autoimmune Diseases. Clin. Dev. Immunol.","DOI":"10.1155\/2013\/535738"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2689","DOI":"10.1128\/jvi.66.5.2689-2697.1992","article-title":"Epstein-Barr virus latent gene transcription in nasopharyngeal carcinoma cells: Coexpression of EBNA1, LMP1, and LMP2 transcripts","volume":"66","author":"Brooks","year":"1992","journal-title":"J. Virol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Ma, S., Tsai, M.H., Romero-Masters, J.C., Ranheim, E.A., Huebner, S.M., Bristol, J.A., Delecluse, H.J., and Kenney, S.C. (2017). Latent Membrane Protein 1 (LMP1) and LMP2A Collaborate To Promote Epstein-Barr Virus-Induced B Cell Lymphomas in a Cord Blood-Humanized Mouse Model but Are Not Essential. J. Virol., 91.","DOI":"10.1128\/JVI.01928-16"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Wang, L.W., Jiang, S., and Gewurz, B.E. (2017). Epstein-Barr Virus LMP1-Mediated Oncogenicity. J. Virol., 91.","DOI":"10.1128\/JVI.01718-16"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Vrzalikova, K., Sunmonu, T., Reynolds, G., and Murray, P. (2018). Contribution of Epstein-Barr Virus Latent Proteins to the Pathogenesis of Classical Hodgkin Lymphoma. Pathogens, 7.","DOI":"10.3390\/pathogens7030059"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2319","DOI":"10.1128\/jvi.64.5.2319-2326.1990","article-title":"A second Epstein-Barr virus membrane protein (LMP2) is expressed in latent infection and colocalizes with LMP1","volume":"64","author":"Longnecker","year":"1990","journal-title":"J. Virol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"265","DOI":"10.3389\/fonc.2018.00265","article-title":"Epstein\u2013Barr Virus-Associated Malignancies: Roles of Viral Oncoproteins in Carcinogenesis","volume":"8","author":"Malki","year":"2018","journal-title":"Front. Oncol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1038\/nrc.2016.92","article-title":"Epstein-Barr virus: more than 50 years old and still providing surprises","volume":"16","author":"Young","year":"2016","journal-title":"Nat. Rev. Cancer"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"11612","DOI":"10.1073\/pnas.1514484112","article-title":"Evasion of affinity-based selection in germinal centers by Epstein\u2013Barr virus LMP2A","volume":"112","author":"Minamitani","year":"2015","journal-title":"Proc. Nat.l. Acad. Sci. USA"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1749","DOI":"10.1086\/523813","article-title":"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","volume":"196","author":"Sokal","year":"2017","journal-title":"J. Infect. Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"104","DOI":"10.3389\/fonc.2019.00104","article-title":"Progress in EBV Vaccines","volume":"9","author":"Mautner","year":"2019","journal-title":"Front. Oncol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2642","DOI":"10.1002\/cncr.30541","article-title":"Epstein-Barr virus-specific adoptive immunotherapy for recurrent, metastatic nasopharyngeal carcinoma","volume":"123","author":"Huang","year":"2017","journal-title":"Cancer"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1038\/mt.2013.242","article-title":"Adoptive T-cell transfer and chemotherapy in the first-line treatment of metastatic and\/or locally recurrent nasopharyngeal carcinoma","volume":"22","author":"Chia","year":"2014","journal-title":"Mol. Ther."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2078","DOI":"10.1016\/S0140-6736(15)00239-1","article-title":"Safety, efficacy, and immunogenicity of VGX-3100, a therapeutic synthetic DNA vaccine targeting human papillomavirus 16 and 18 E6 and E7 proteins for cervical intraepithelial neoplasia 2\/3: A randomised, double-blind, placebo-controlled phase 2b trial","volume":"386","author":"Trimble","year":"2015","journal-title":"Lancet"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1158\/1078-0432.CCR-18-1763","article-title":"Immunotherapy Targeting HPV16\/18 Generates Potent Immune Responses in HPV-Associated Head and Neck Cancer","volume":"25","author":"Aggarwal","year":"2019","journal-title":"Clin. Cancer Res."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Lin, M.C., Lin, Y.C., Chen, S.T., Young, T.H., and Lou, P.J. (2017). Therapeutic vaccine targeting Epstein-Barr virus latent protein, LMP1, suppresses LMP1-expressing tumor growth and metastasis in vivo. BMC Cancer, 17.","DOI":"10.1186\/s12885-016-3027-1"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"117","DOI":"10.5114\/ceji.2018.77379","article-title":"CD40L-adjuvanted DNA vaccine carrying EBV-LMP2 antigen enhances anti-tumor effect in NPC transplantation tumor animal","volume":"43","author":"Lei","year":"2018","journal-title":"Cent. Eur. J. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1038\/375685a0","article-title":"Inhibition of antigen processing by the internal repeat region of the Epstein-Barr virus nuclear antigen-1","volume":"375","author":"Levitskaya","year":"1995","journal-title":"Nature"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1126\/science.1088902","article-title":"Self-inhibition of synthesis and antigen presentation by Epstein-Barr virus-encoded EBNA1","volume":"301","author":"Yin","year":"2003","journal-title":"Science"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1128\/JVI.01369-08","article-title":"mRNA translation regulation by the Gly-Ala repeat of Epstein-Barr virus nuclear antigen 1","volume":"83","author":"Apcher","year":"2009","journal-title":"J. Virol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.molcel.2005.02.029","article-title":"Structure of the p53 binding domain of HAUSP\/USP7 bound to Epstein-Barr nuclear antigen 1 implications for EBV-mediated immortalization","volume":"18","author":"Saridakis","year":"2005","journal-title":"Mol. Cell"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"5614","DOI":"10.1038\/sj.onc.1206497","article-title":"Ubiquitination of the Epstein-Barr virus-encoded latent membrane protein 1 depends on the integrity of the TRAF binding site","volume":"22","author":"Rothenberger","year":"2003","journal-title":"Oncogene"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1851","DOI":"10.1038\/sj.onc.1201359","article-title":"Epstein-Barr virus latent membrane protein-1 (LMP1) C-terminus activation region 2 (CTAR2) maps to the far C-terminus and requires oligomerisation for NF-kappaB activation","volume":"15","author":"Floettmann","year":"1997","journal-title":"Oncogene"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"8526","DOI":"10.1128\/MCB.20.22.8526-8535.2000","article-title":"Latent membrane protein 2A of Epstein-Barr virus binds WW domain E3 protein-ubiquitin ligases that ubiquitinate B-cell tyrosine kinases","volume":"20","author":"Winberg","year":"2000","journal-title":"Mol. Cell. Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1006\/viro.1999.0166","article-title":"The Epstein-Barr virus latent membrane protein 2A PY motif recruits WW domain-containing ubiquitin-protein ligases","volume":"268","author":"Ikeda","year":"2000","journal-title":"Virology"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"7796","DOI":"10.1128\/JVI.72.10.7796-7806.1998","article-title":"Tyrosine 112 of latent membrane protein 2A is essential for protein tyrosine kinase loading and regulation of Epstein-Barr virus latency","volume":"72","author":"Fruehling","year":"1998","journal-title":"J. Virol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"10308","DOI":"10.1128\/JVI.00853-12","article-title":"Epstein-Barr virus latent membrane protein-2A induces ITAM\/Syk- and Akt-dependent epithelial migration through \u03b1v-integrin membrane translocation","volume":"86","author":"Fotheringham","year":"2012","journal-title":"J. Virol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Muthumani, K., Falzarano, D., Reuschel, E.L., Tingey, C., Flingai, S., Villarreal, D.O., Wise, M., Patel, A., Izmirly, A., and Aljuaid, A. (2015). A synthetic consensus anti\u2013spike protein DNA vaccine induces protective immunity against Middle East respiratory syndrome coronavirus in nonhuman primates. Sci. Transl. Med., 7.","DOI":"10.1126\/scitranslmed.aac7462"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1774","DOI":"10.1016\/j.celrep.2016.01.056","article-title":"Satb1 Overexpression Drives Tumor-Promoting Activities in Cancer-Associated Dendritic Cells","volume":"14","author":"Tesone","year":"2016","journal-title":"Cell Rep."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/j.ymthe.2018.11.014","article-title":"Engineered DNA Vaccination against Follicle-Stimulating Hormone Receptor Delays Ovarian Cancer Progression in Animal Models","volume":"27","author":"Wojtak","year":"2019","journal-title":"Mol. Ther."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1158\/2326-6066.CIR-18-0283","article-title":"A Synthetic DNA, Multi-Neoantigen Vaccine Drives Predominately MHC Class I CD8+ T-cell Responses, Impacting Tumor Challenge","volume":"7","author":"Duperret","year":"2019","journal-title":"Cancer Immunol. Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"6015","DOI":"10.1158\/1078-0432.CCR-18-1013","article-title":"A Designer Cross-reactive DNA Immunotherapeutic Vaccine that Targets Multiple MAGE-A Family Members Simultaneously for Cancer Therapy","volume":"24","author":"Duperret","year":"2018","journal-title":"Clin. Cancer Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e1515058","DOI":"10.1080\/2162402X.2018.1515058","article-title":"IL-33 delays metastatic peritoneal cancer progression inducing an allergic microenvironment","volume":"8","author":"Svoronos","year":"2019","journal-title":"Oncoimmunology"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Choi, H., Kudchodkar, S.B., Reuschel, E.L., Asija, K., Borole, P., Ho, M., Wojtak, K., Reed, C., Ramos, S., and Bopp, N.E. (2019). Protective immunity by an engineered DNA vaccine for Mayaro virus. PLoS Negl. Trop. Dis., 13.","DOI":"10.1371\/journal.pntd.0007042"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.ymthe.2018.10.016","article-title":"Development of Novel DNA-Encoded PCSK9 Monoclonal Antibodies as Lipid-Lowering Therapeutics","volume":"27","author":"Khoshnejad","year":"2019","journal-title":"Mol. Ther."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Wan, Y., Kang, G., Sreenivasan, C., Daharsh, L., Zhang, J., Fan, W., Wang, D., Moriyama, H., Li, F., and Li, Q. (2018). A DNA Vaccine Expressing Consensus Hemagglutinin-Esterase Fusion Protein Protected Guinea Pigs from Infection by Two Lineages of Influenza D Virus. J. Viro., 92.","DOI":"10.1128\/JVI.00110-18"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"10489","DOI":"10.1073\/pnas.0803352105","article-title":"A Centralized Gene-Based HIV-1 Vaccine Elicits Broad Cross-Clade Cellular Immune Responses in Rhesus Monkeys","volume":"105","author":"Santra","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1432","DOI":"10.1038\/mt.2013.61","article-title":"Induction of Broad Cytotoxic T Cells by Protective DNA Vaccination Against Marburg and Ebola","volume":"21","author":"Shedlock","year":"2013","journal-title":"Mol. Ther."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1099\/jgv.0.000699","article-title":"Comparative analysis of 22 Epstein\u2013Barr virus genomes from diseased and healthy individuals","volume":"98","author":"Zhou","year":"2017","journal-title":"J. Gen. Virol."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Tebas, P., Kraynyak, K.A., Patel, A., Maslow, J.N., Morrow, M.P., Sylvester, A.J., Knoblock, D., Gillespie, E., Amante, D., and Racine, T. (2019). Intradermal SynCon\u00ae Ebola GP DNA Vaccine is Temperature Stable and Safely Demonstrates Cellular and Humoral Immunogenicity Advantages in Healthy Volunteers. J. Infect. Dis.","DOI":"10.1093\/infdis\/jiz132"},{"key":"ref_53","unstructured":"Tebas, P., Roberts, C.C., Muthumani, K., Reuschel, E.L., Kudchodkar, S.B., Zaidi, F.I., White, S., Khan, A.S., Racine, T., and Choi, H. (2017). Safety and Immunogenicity of an Anti-Zika Virus DNA Vaccine\u2015Preliminary Report. N. Engl. J. Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1002\/path.1569","article-title":"Expression of the Epstein-Barr virus (EBV)-encoded latent membrane protein 2A (LMP2A) in EBV-associated nasopharyngeal carcinoma","volume":"203","author":"Heussinger","year":"2004","journal-title":"J. Pathol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1080\/14760584.2017.1293529","article-title":"Designing an effective vaccine to prevent Epstein-Barr virus-associated diseases: Challenges and opportunities","volume":"16","author":"Dasari","year":"2017","journal-title":"Expert Rev. Vaccines"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1186\/1750-9378-9-38","article-title":"Global burden of deaths from Epstein-Barr virus attributable malignancies 1990\u20132010","volume":"9","author":"Khan","year":"2014","journal-title":"Infect. Agent Cancer"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"8942","DOI":"10.1200\/JCO.2005.02.6195","article-title":"Cell Therapy of Stage IV Nasopharyngeal Carcinoma With Autologous Epstein-Barr Virus\u2013Targeted Cytotoxic T Lymphocytes","volume":"23","author":"Comoli","year":"2005","journal-title":"J. Clin. Oncol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1158\/0008-5472.CAN-11-3399","article-title":"Effective treatment of metastatic forms of Epstein-Barr virus-associated nasopharyngeal carcinoma with a novel adenovirus-based adoptive immunotherapy","volume":"72","author":"Smith","year":"2012","journal-title":"Cancer Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1200\/JCO.2011.39.8495","article-title":"Adoptive Transfer of Epstein-Barr Virus (EBV) Nuclear Antigen 1\u2013Specific T Cells As Treatment for EBV Reactivation and Lymphoproliferative Disorders After Allogeneic Stem-Cell Transplantation","volume":"31","author":"Icheva","year":"2013","journal-title":"J. Clin. Oncol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1200\/JCO.2013.51.5304","article-title":"Sustained Complete Responses in Patients With Lymphoma Receiving Autologous Cytotoxic T Lymphocytes Targeting Epstein-Barr Virus Latent Membrane Proteins","volume":"32","author":"Bollard","year":"2014","journal-title":"J. Clin. Oncol."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Pender, M.P., Csurhes, P.A., Smith, C., Douglas, N.L., Neller, M.A., Matthews, K.K., Beagley, L., Rehan, S., Crooks, P., and Hopkins, T.J. (2018). Epstein-Barr virus-specific T cell therapy for progressive multiple sclerosis. JCI Insight, 3.","DOI":"10.1172\/jci.insight.124714"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/S1044579X02000858","article-title":"Epidemiology of nasopharyngeal carcinoma","volume":"12","author":"Yu","year":"2002","journal-title":"Semin.n Cancer Biol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2071","DOI":"10.1172\/JCI125364","article-title":"Heterologous prime-boost vaccination protects against EBV antigen-expressing lymphomas","volume":"129","author":"Citterio","year":"2019","journal-title":"J. Clin. Invest."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"13","DOI":"10.18632\/oncotarget.26535","article-title":"Simplifying checkpoint inhibitor delivery through in vivo generation of synthetic DNA-encoded monoclonal antibodies (DMAbs)","volume":"10","author":"Duperret","year":"2019","journal-title":"Oncotarget"}],"container-title":["Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-393X\/7\/2\/44\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:54:43Z","timestamp":1760187283000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-393X\/7\/2\/44"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,5,24]]},"references-count":64,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2019,6]]}},"alternative-id":["vaccines7020044"],"URL":"https:\/\/doi.org\/10.3390\/vaccines7020044","relation":{},"ISSN":["2076-393X"],"issn-type":[{"value":"2076-393X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,5,24]]}}}