Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

Infusing virus-specific T cells is effective treatment for rare Epstein-Barr virus (EBV)-associated posttransplant lymphomas, and more limited success has been reported using this approach to treat a far more common EBV-associated malignancy, nasopharyngeal carcinoma (NPC). However, current approaches using EBV-transformed lymphoblastoid cell lines to reactivate EBV-specific T cells for infusion take 2 to 3 months of in vitro culture and favor outgrowth of T cells targeting viral antigens expressed within EBV(+) lymphomas, but not in NPC. Here, we explore T-cell receptor (TCR) gene transfer to rapidly and reliably generate T cells specific for the NPC-associated viral protein LMP2. We cloned a human leukocyte antigen (HLA) A*1101-restricted TCR, which would be widely applicable because 40% of NPC patients carry this HLA allele. Studying both the wild-type and modified forms, we have optimized expression of the TCR and demonstrated high-avidity antigen-specific function (proliferation, cytotoxicity, and cytokine release) in both CD8(+) and CD4(+) T cells. The engineered T cells also inhibited LMP2(+) epithelial tumor growth in a mouse model. Furthermore, transduced T cells from patients with advanced NPC lysed LMP2-expressing NPC cell lines. Using this approach, within a few days large numbers of high-avidity LMP2-specific T cells can be generated reliably to treat NPC, thus providing an ideal clinical setting to test TCR gene transfer without the risk of autoimmunity through targeting self-antigens.

Original publication




Journal article


Cancer immunology research

Publication Date





1138 - 1147


School of Cancer Sciences, Cancer Immunology & Immunotherapy Centre (CIIC), University of Birmingham, Edgbaston, Birmingham, United Kingdom.


CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Cell Line, Tumor, Animals, Humans, Mice, Herpesvirus 4, Human, Epstein-Barr Virus Infections, Carcinoma, Nasopharyngeal Neoplasms, Disease Models, Animal, Receptors, Antigen, T-Cell, Viral Matrix Proteins, HLA-A Antigens, Epitopes, T-Lymphocyte, Cytokines, Immunotherapy, Tumor Burden, Xenograft Model Antitumor Assays, Gene Transfer Techniques, Transduction, Genetic, Cytotoxicity, Immunologic, Gene Expression, Molecular Sequence Data, Female, Interferon-gamma, Nasopharyngeal Carcinoma