Induction of specific CTL by MAGE-3/CEA peptide-pulsed dendritic cells from HLA-A2/A24(+) gastrointestinal cancer patients

J Cancer Res Clin Oncol. 2002 Sep;128(9):507-15. doi: 10.1007/s00432-002-0358-x. Epub 2002 Aug 21.

Abstract

Purpose: In this study, we aimed to investigate whether MAGE3/CEA peptide-pulsed dendritic cells could induce specific cytotoxic T lymphocytes (CTL).

Methods: In this pilot study, we selected 25 patients expressing MAGE-3-HLA-A2/A24 or CEA-HLA-A24. Patients' dendritic cells (DCs) were expanded in vitro in the presence of recombined-human granular macrophage colony stimulating factor (rhGM-CSF) and recombined-human interleukin 4 (rhIL-4), pulsed with MAGE-3/CEA (HLA-A2/A24) peptide. The cytolytic cells' activity, induced by peptide-pulsed DCs and unpurified T cells as effector cells, and with Mel526, 803, Raji, and K562 as target cells, were measured using LDH-releasing assay.

Results: DCs were obtained by in vitro expansion in all cases although DC harvest rates varied among different patients (7.1+/-3.2%). Compared with T-IL-2 (IL-2-induced T cells), T-DC-P - which resulted from T-IL-2 co-cultured with DCs pulsed by MAGE3 or CEA peptides - exhibited an increase in cytolytic activity against Mel526 (expressing MAGE-3-HLA-A2) and 803 (expressing CEA-HLA-A24) cell lines by about 25-30% ( P<0.01). In contrast, there was no significant difference between the activity against Raji and K562 cells, which are negative for both peptides.

Conclusions: This study showed that combined usage of rhGM-CSF and rhIL-4 in vitro could expand DCs, and that the DCs pulsed with specific peptides could induce MAGE- and CEA-specific CTL responses. The DC-based vaccine may provide an important method for the immunological treatment of gastrointestinal cancers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antigens, Neoplasm / immunology*
  • Carcinoembryonic Antigen / immunology*
  • Cytotoxicity Tests, Immunologic
  • Dendritic Cells / immunology*
  • Female
  • Gastrointestinal Neoplasms / immunology*
  • HLA-A Antigens / immunology*
  • HLA-A2 Antigen / immunology*
  • HLA-A24 Antigen
  • Humans
  • Lymphocyte Activation*
  • Male
  • Middle Aged
  • Neoplasm Proteins / immunology*
  • Peptides / immunology
  • T-Lymphocytes, Cytotoxic / immunology*

Substances

  • Antigens, Neoplasm
  • Carcinoembryonic Antigen
  • HLA-A Antigens
  • HLA-A2 Antigen
  • HLA-A24 Antigen
  • MAGEA3 protein, human
  • Neoplasm Proteins
  • Peptides