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 carcinoma.
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.
Lin
Chen-Lung
CL
Department of Surgery, Chang Gung Memorial Hospital, Kaohsiung, 883 Taiwan. clin@hkucc.hku.hk
Lo
Wei-Feng
WF
Lee
Tzong-Hsien
TH
Ren
Yi
Y
Hwang
Shiuh-Lin
SL
Cheng
Yu-Fan
YF
Chen
Chao-Long
CL
Chang
Yu-Sen
YS
Lee
Steve P
SP
Rickinson
Alan B
AB
Tam
Paul Kwong Hang
PK
D000328:Adult; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D015788:HLA-A1 Antigen / Q000276:immunology; D004854:Herpesvirus 4, Human; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000276:immunology* / Q000628:therapy* / Q000821:virology; D014763:Viral Matrix Proteins / Q000276:immunology*
C037662:EBV-associated membrane antigen, Epstein-Barr virus; D015788:HLA-A1 Antigen; D014763:Viral Matrix Proteins; D007371:Interferon-gamma