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, pulse...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 2002-12, Vol.62 (23), p.6952-6958
Main Authors: LIN, Chen-Lung, LO, Wei-Feng, KWONG HANG TAM, Paul, LEE, Tzong-Hsien, YI REN, HWANG, Shiuh-Lin, CHENG, Yu-Fan, CHEN, Chao-Long, CHANG, Yu-Sen, LEE, Steve P, RICKINSON, Alan B
Format: Article
Language:English
Subjects:
Adult
Antineoplastic agents
Biological and medical sciences
CD8-Positive T-Lymphocytes - immunology
CD8-Positive T-Lymphocytes - metabolism
Cytotoxicity, Immunologic
Dendritic Cells - immunology
Female
Herpesvirus 4, Human
HLA-A1 Antigen - immunology
Humans
Immunotherapy
Immunotherapy, Adoptive - methods
Interferon-gamma - biosynthesis
Lymphocyte Activation - immunology
Male
Medical sciences
Middle Aged
Nasopharyngeal Neoplasms - immunology
Nasopharyngeal Neoplasms - therapy
Nasopharyngeal Neoplasms - virology
Pharmacology. Drug treatments
Viral Matrix Proteins - immunology
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Summary: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.
ISSN:0008-5472
1538-7445