Human Leukocyte Antigen (HLA) A*1101-restricted Epstein-Barr Virus-specific T-cell Receptor Gene Transfer to Target Nasopharyngeal Carcinoma

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