title: Evaluation of Epstein-Barr virus latent membrane protein 2 specific T-cell receptors driven by T-cell specific promoters using lentiviral vector.
abstract: Transduction of latent membrane protein 2 (LMP2)-specific T-cell receptors into activated T lymphocytes may provide a universal, MHC-restricted mean to treat EBV-associated tumors in adoptive immunotherapy. We compared TCR-specific promoters of distinct origin in lentiviral vectors, that is, Vβ6.7, delta, luria, and Vβ5.1 to evaluate TCR gene expression in human primary peripheral blood monocytes and T cell line HSB2. Vectors containing Vβ 6.7 promoter were found to be optimal for expression in PBMCs, and they maintained expression of the transduced TCRs for up to 7 weeks. These cells had the potential to recognize subdominant EBV latency antigens as measured by cytotoxicity and IFN-γ secretion. The nude mice also exhibited significant resistance to the HLA-A2 and LMP2-positive CNE tumor cell challenge after being infused with lentiviral transduced CTLs. In conclusion, LMP2-specific CTLs by lentiviral transduction have the potential use for treatment of EBV-related tumors.
authors.affiliation: Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province, Nanjing 210029, China.
authors.forename: Dongchang
authors.initials: D
authors.lastname: Yang
authors.forename: Qing
authors.initials: Q
authors.lastname: Shao
authors.forename: Hua
authors.initials: H
authors.lastname: Sun
authors.forename: Xiaoxin
authors.initials: X
authors.lastname: Mu
authors.forename: Yun
authors.initials: Y
authors.lastname: Gao
authors.forename: Runqiu
authors.initials: R
authors.lastname: Jiang
authors.forename: Jiajie
authors.initials: J
authors.lastname: Hou
authors.forename: Kun
authors.initials: K
authors.lastname: Yao
authors.forename: Yun
authors.initials: Y
authors.lastname: Chen
authors.forename: Beicheng
authors.initials: B
authors.lastname: Sun
mesh_terms: D000818:Animals; D002277:Carcinoma; D002460:Cell Line; D020031:Epstein-Barr Virus Infections / Q000276:immunology / Q000628:therapy / Q000821:virology; D005822:Genetic Vectors; D015789:HLA-A2 Antigen / Q000235:genetics / Q000378:metabolism; D004854:Herpesvirus 4, Human / Q000276:immunology; D006801:Humans; D016219:Immunotherapy, Adoptive; D016086:Lentivirus / Q000235:genetics*; D051379:Mice; D008819:Mice, Nude; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000628:therapy; D011401:Promoter Regions, Genetic; D011948:Receptors, Antigen, T-Cell / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000821:virology; D014161:Transduction, Genetic; D014763:Viral Matrix Proteins / Q000276:immunology / Q000378:metabolism*
chemical_list: C037662:EBV-associated membrane antigen, Epstein-Barr virus; D015789:HLA-A2 Antigen; D011948:Receptors, Antigen, T-Cell; D014763:Viral Matrix Proteins