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你可以从这个文件学习关于免疫识别和免疫攻击.[StephenW]
http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6W7C-51J363G-6&_user=10&_coverDate=11%2F23%2F2010&_rdoc=1&_fmt=high&_orig=search&_origin=search&_sort=d&_docanchor=&view=c&_searchStrId=1631130261&_rerunOrigin=google&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=9760dee963ff9573d6de94fb316c35ef&searchtype=a
Engineering Virus-specific T cells that Target HBV Infected Hepatocytes and Hepatocellular Carcinoma Cell Lines
References and further reading may be available for this article. To view references and further reading you must purchase this article.
Adam J. Gehringa, Shao-An Xueb, Zi Zong Hoa, Denise Teoha, Christiane Ruedlc, Adeline Chiaa, Sarene Koha, d, Seng Gee Lime, Mala K. Mainif, Hans Staussb and Antonio Bertolettia, e, g, , ,
a Singapore Institute for Clinical Sciences, Agency for Science Technology and Research, (A*STAR), Singapore
b Department of Immunology, Royal Free Hospital, Royal Free and University College Medical School, London, UK
c Division of Molecular & Cell Biology, Nanyang Technological University, Singapore
d Department of Laboratory Medicine, Division of Clinical Microbiology, Karolinska Institute, Stockholm, Sweden
e Yong Loo Lin School of Medicine, National University of Singapore, Singapore
f Division of Infection and Immunity, University College London, UK
g Duke-NUS Medical School, Singapore
Received 13 May 2010;
revised 1 October 2010;
accepted 20 October 2010.
Available online 23 November 2010.
AbstractBackground & AimsVirus-specific T cells capable of controlling HBV and eliminating hepatocellular carcinoma (HCC) expressing HBV antigens are deleted or dysfunctional in patients with chronic HBV or HBV-related HCC. The goal of this study was to determine if T cell receptor (TCR) gene transfer can reconstitute HBV specific T cell immunity in lymphocytes of chronic HBV patients and investigate whether HCC cells with natural HBV-DNA integration can be recognized by genetically modified T cells.
MethodsWe used vector-mediated gene transfer to introduce HLA-A2-restricted, HBV-specific TCRs into T cells of chronic HBV as well as HBV-related HCC patients.
ResultsThe introduced TCRs were expressed on the cell surface, evidenced by Vβ and pentamer staining. TCR transduced T cells produced IFN-γ, TNF-α, IL-2, and lysed HBV infected hepatocyte-like cell lines. Furthermore, HCC cell lines with natural HBV-DNA integration could be recognized by HBV-specific TCR-redirected T cells.
ConclusionTCR re-directed HBV-specific T cells generated from PBMC of chronic HBV and HBV-related HCC patients were multifunctional and capable of recognizing HBV infected cells and HCC tumor cells expressing viral antigens from naturally integrated HBV DNA. These genetically modified T cells could be used to reconstitute virus-specific T cell immunity in chronic HBV patients and target tumors in HBV-related HCC.
Keywords: Immunotherapy; T cell receptor gene transfer; Hepatocellular carcinoma; Hepatitis B virus
Corresponding author.
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Journal of Hepatology |
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