Evaluation of Epstein-Barr Virus Latent Membrane Protein 2 Specific T-Cell Receptors Driven by T-Cell Specific Promoters Using Lentiviral Vector

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,...

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Main Authors: Dongchang Yang, Qing Shao, Hua Sun, Xiaoxin Mu, Yun Gao, Runqiu Jiang, Jiajie Hou, Kun Yao, Yun Chen, Beicheng Sun
Format: Article
Language:English
Published: Wiley 2011-01-01
Series:Clinical and Developmental Immunology
Online Access:http://dx.doi.org/10.1155/2011/716926
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author Dongchang Yang
Qing Shao
Hua Sun
Xiaoxin Mu
Yun Gao
Runqiu Jiang
Jiajie Hou
Kun Yao
Yun Chen
Beicheng Sun
author_facet Dongchang Yang
Qing Shao
Hua Sun
Xiaoxin Mu
Yun Gao
Runqiu Jiang
Jiajie Hou
Kun Yao
Yun Chen
Beicheng Sun
author_sort Dongchang Yang
collection DOAJ
description 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.
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institution Kabale University
issn 1740-2522
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language English
publishDate 2011-01-01
publisher Wiley
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series Clinical and Developmental Immunology
spelling doaj-art-3f7914f3eb564f91b3d0cd0000709ab52025-02-03T06:14:14ZengWileyClinical and Developmental Immunology1740-25221740-25302011-01-01201110.1155/2011/716926716926Evaluation of Epstein-Barr Virus Latent Membrane Protein 2 Specific T-Cell Receptors Driven by T-Cell Specific Promoters Using Lentiviral VectorDongchang Yang0Qing Shao1Hua Sun2Xiaoxin Mu3Yun Gao4Runqiu Jiang5Jiajie Hou6Kun Yao7Yun Chen8Beicheng Sun9Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province, Nanjing 210029, ChinaDepartment of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province, Nanjing 210029, ChinaBrown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center at Houston, Houston, TX 77030, USALiver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province, Nanjing 210029, ChinaLiver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province, Nanjing 210029, ChinaLiver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province, Nanjing 210029, ChinaLiver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province, Nanjing 210029, ChinaDepartment of Microbiology and Immunology, Nanjing Medical University, Nanjing 210029, ChinaLiver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province, Nanjing 210029, ChinaLiver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province, Nanjing 210029, ChinaTransduction 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.http://dx.doi.org/10.1155/2011/716926
spellingShingle Dongchang Yang
Qing Shao
Hua Sun
Xiaoxin Mu
Yun Gao
Runqiu Jiang
Jiajie Hou
Kun Yao
Yun Chen
Beicheng Sun
Evaluation of Epstein-Barr Virus Latent Membrane Protein 2 Specific T-Cell Receptors Driven by T-Cell Specific Promoters Using Lentiviral Vector
Clinical and Developmental Immunology
title Evaluation of Epstein-Barr Virus Latent Membrane Protein 2 Specific T-Cell Receptors Driven by T-Cell Specific Promoters Using Lentiviral Vector
title_full Evaluation of Epstein-Barr Virus Latent Membrane Protein 2 Specific T-Cell Receptors Driven by T-Cell Specific Promoters Using Lentiviral Vector
title_fullStr Evaluation of Epstein-Barr Virus Latent Membrane Protein 2 Specific T-Cell Receptors Driven by T-Cell Specific Promoters Using Lentiviral Vector
title_full_unstemmed Evaluation of Epstein-Barr Virus Latent Membrane Protein 2 Specific T-Cell Receptors Driven by T-Cell Specific Promoters Using Lentiviral Vector
title_short Evaluation of Epstein-Barr Virus Latent Membrane Protein 2 Specific T-Cell Receptors Driven by T-Cell Specific Promoters Using Lentiviral Vector
title_sort evaluation of epstein barr virus latent membrane protein 2 specific t cell receptors driven by t cell specific promoters using lentiviral vector
url http://dx.doi.org/10.1155/2011/716926
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