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: Dongchang Yang, Qing Shao, Hua Sun, Xiaoxin Mu, Yun Gao, Runqiu Jiang, Jiajie Hou, Kun Yao, Yun Chen, Beicheng Sun
• Journal: Clinical & developmental immunology (Clin Dev Immunol) Vol. 2011 Pg. 716926 ( 2011) ISSN: 1740-2530 [Electronic] Egypt
• PMID: 21969838 (Publication Type: Evaluation Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• EBV-associated membrane antigen, Epstein-Barr virus
• HLA-A2 Antigen
• Receptors, Antigen, T-Cell
• Viral Matrix Proteins

Topics

• Animals
• Carcinoma
• Cell Line
• Epstein-Barr Virus Infections (immunology, therapy, virology)
• Genetic Vectors
• HLA-A2 Antigen (genetics, metabolism)
• Herpesvirus 4, Human (immunology)
• Humans
• Immunotherapy, Adoptive
• Lentivirus (genetics)
• Mice
• Mice, Nude
• Nasopharyngeal Carcinoma
• Nasopharyngeal Neoplasms (therapy)
• Promoter Regions, Genetic
• Receptors, Antigen, T-Cell (classification, genetics, metabolism)
• T-Lymphocytes (immunology, metabolism, virology)
• T-Lymphocytes, Cytotoxic (immunology, virology)
• Transduction, Genetic
• Viral Matrix Proteins (immunology, metabolism)