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Immunization with Epstein-Barr Virus (EBV) Peptide-pulsed Dendritic Cells Induces Functional CD8+ T-Cell Immunity and May Lead to Tumor Regression in Patients with EBV-positive Nasopharyngeal Carcinoma¹

Department of Surgery, Chang Gung Memorial Hospital, Kaohsiung, 883 Taiwan [C-L. L., W-F. L., T-H. L., C-L. C.]; Department of Surgery, The University of Hong Kong Medical Centre, Queen Mary Hospital, Pokfulam Road, Hong Kong, SAR, China [C-L. L., Y. R., P. K. H. T.]; Department of Surgery, Kaohsiung Medical University, Kaohsiung, 807 Taiwan [S-L. H.]; Department of Radiology, Chang Gung Memorial Hospital, Kaohsiung, 883 Taiwan [Y-F. C.]; Graduate Institute of Basic Medical Sciences, Chang Gung University, Tao-Yuan, 333 Taiwan [Y-S. C.]; and CRC Institute for Cancer Studies, Medical School, University of Birmingham, Edgbaston, Birmingham, B15 2TT United Kingdom [S. P. L., A. B. R.]

Nasopharyngeal carcinoma (NPC), a common neoplasm in Southeast Asia, is EBV-positive and expresses a limited number of antigens, including latent membrane protein 2. In this study, autologous monocyte-derived dendritic cells were cultured from patients with advanced NPC, matured with cytokine, pulsed with HLA-A1101-, A2402-, or B40011-restricted epitope peptides from EBV latent membrane protein 2 and injected into inguinal lymph nodes. Sixteen patients with local recurrence or distant metastasis after conventional therapies received four injections at weekly intervals. Epitope-specific CD8+ T-cell responses were elicited or boosted in 9 patients receiving HLA-A1101- or A2402-restricted peptides, with stronger responses seen to the A1101 peptide. Furthermore, epitope-specific cytotoxicity was detectable in peripheral blood T cells harvested at 3-months after vaccination from A1101-responsive patients, and in 2 patients, this coincided with partial tumor reduction. Approaches leading to stronger and more sustained EBV-specific T-cell responses, therefore, may have therapeutic potential in the context of NPC.

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