title: Therapeutic vaccine targeting Epstein-Barr virus latent protein, LMP1, suppresses LMP1-expressing tumor growth and metastasis in vivo.
abstract: In endemic area, nasopharyngeal carcinoma (NPC) tumor cells harbor EBV latent infection and expresses viral antigens such as EBNA1, LMP1 and LMP2. In this study, we established a NPC-mimicry animal model and assessed the therapeutic potential of LMP1 vaccine.
  
  
  
  Animal models were established by injection of LMP1-expressing TC-1 cells in C57BL6/J mice subcutaneously or through tail veins. pcDNA3.1 empty vector or LMP1/pcDNA3.1 vaccine was delivered by a helium-driven gene gun. Effectiveness of vaccine was evaluated by measuring the tumor size and numbers of metastatic lung nodules. Circulating cytokines were evaluated by ELISArray. Populations of activated cytotoxic T lymphocytes (CTLs) and LMP1-specific T lymphocytes were evaluated by flow cytometry with CD8/CD107a double staining and interferon-γ ELISPOT assay, respectively.
  
  
  
  LMP1 vaccine significantly suppressed tumor growth (n = 3) and metastasis (n = 4) in vivo. When vaccinated before tumor challenge, all mice in vaccine group were tumor-free, whereas all mice in the control group developed tumors within 2 weeks after tumor challenge (n = 10). Cytokine ELISArray revealed elevation of a panel of proinflammatory cytokines in mice receiving LMP1 vaccine. Flow cytometry and interferon-γ ELISPOT assay revealed that LMP1 vaccine induced larger populations of activated CTLs and LMP1-specific T lymphocytes.
  
  
  
  This pre-clinical study provides a promising result that LMP1 vaccine suppresses LMP1-expressing tumor growth and metastasis in vivo.
authors.affiliation: Department of Otolaryngology, National Taiwan University Hospital, Hsin-Chu Branch, No. 25, Lane 442, Sec. 1, Jingguo Road, Hsinchu City, 300, Taiwan.|Graduate Institute of Anatomy and Cell Biology, National Taiwan University College of Medicine, No. 1, Sec. 1, Jen-Ai Road, Taipei, 100, Taiwan.
authors.forename: Mei-Chun
authors.initials: MC
authors.lastname: Lin
authors.affiliation: Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, No. 1, Sec. 1, Jen-Ai Road, Taipei, 100, Taiwan.
authors.forename: Yong-Chong
authors.initials: YC
authors.lastname: Lin
authors.affiliation: Graduate Institute of Anatomy and Cell Biology, National Taiwan University College of Medicine, No. 1, Sec. 1, Jen-Ai Road, Taipei, 100, Taiwan.
authors.forename: Syue-Ting
authors.initials: ST
authors.lastname: Chen
authors.affiliation: Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, No. 1, Sec. 1, Jen-Ai Road, Taipei, 100, Taiwan. thyoung@ntu.edu.tw.
authors.forename: Tai-Horng
authors.initials: TH
authors.lastname: Young
authors.affiliation: Graduate Institute of Anatomy and Cell Biology, National Taiwan University College of Medicine, No. 1, Sec. 1, Jen-Ai Road, Taipei, 100, Taiwan. pjlou@ntu.edu.tw.|Department of Otolaryngology, National Taiwan University Hospital and College of Medicine, No. 7, Chung-Shan South Road, Taipei, 100, Taiwan. pjlou@ntu.edu.tw.
authors.forename: Pei-Jen
authors.initials: PJ
authors.lastname: Lou
mesh_terms: D000818:Animals; D015153:Blotting, Western; D019496:Cancer Vaccines / Q000276:immunology*; D002277:Carcinoma / Q000473:pathology / Q000821:virology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D058501:Enzyme-Linked Immunospot Assay; D020031:Epstein-Barr Virus Infections / Q000150:complications / Q000276:immunology / Q000473:pathology*; D005434:Flow Cytometry; D022283:Herpesvirus Vaccines / Q000276:immunology*; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000473:pathology / Q000821:virology; D014412:Tumor Virus Infections / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology; D014763:Viral Matrix Proteins / Q000276:immunology*
chemical_list: D019496:Cancer Vaccines; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D022283:Herpesvirus Vaccines; D019444:Vaccines, DNA; D014763:Viral Matrix Proteins
keywords: Cytotoxic T lymphocyte (CTL); DNA vaccine; Epstein-Barr virus (EBV); Latent membrane protein 1 (LMP1); Nasopharyngeal carcinoma (NPC)