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

Cancer Res. 2002 Dec 1;62(23):6952-8.

Abstract

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.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Cytotoxicity, Immunologic
  • Dendritic Cells / immunology*
  • Female
  • HLA-A1 Antigen / immunology
  • Herpesvirus 4, Human*
  • Humans
  • Immunotherapy, Adoptive / methods*
  • Interferon-gamma / biosynthesis
  • Lymphocyte Activation / immunology
  • Male
  • Middle Aged
  • Nasopharyngeal Neoplasms / immunology*
  • Nasopharyngeal Neoplasms / therapy*
  • Nasopharyngeal Neoplasms / virology
  • Viral Matrix Proteins / immunology*

Substances

  • EBV-associated membrane antigen, Epstein-Barr virus
  • HLA-A1 Antigen
  • Viral Matrix Proteins
  • Interferon-gamma