Dendritic cells acquire the MAGE-3 human tumor antigen from apoptotic cells and induce a class I-restricted T cell response

Proc Natl Acad Sci U S A. 2000 Feb 29;97(5):2185-90. doi: 10.1073/pnas.040540197.

Abstract

In an attempt to transduce monocyte-derived dendritic cells (DCs) with a retroviral vector coding for an intracytoplasmic tumor antigen (TAA), we were confronted by the evident dissociation between the ability of the treated DCs to induce a TAA-specific response, and the presence of integrated vector proviral DNA. The TAA, i.e., MAGE-3, was acquired by DCs and presented to immune effectors, thanks to the property of DCs to uptake the apoptotic bodies released by the irradiated vector-producing cells. Indeed, we observed that upon irradiation vector-producing cells underwent apoptotic cell death, monitored by annexin V and propidium iodide staining, and were phagocytosed by DCs. Lymphocytes obtained from a patient affected by a MAGE-3(+) melanoma, were stimulated in vitro with autologous DCs previously exposed to irradiated MAGE-3-expressing cells. This procedure led to the induction of MAGE-3-specific cytotoxic effectors, directed against a yet unknown MAGE-3 epitope presented by HLA-A*B5201 molecules. These data demonstrate that DCs can present engulfed human TAAs, thus providing strategies for cancer vaccination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Animals
  • Antigens, Neoplasm / immunology*
  • Apoptosis / immunology*
  • COS Cells
  • Dendritic Cells / immunology*
  • Genetic Vectors
  • HLA-B Antigens / immunology*
  • HLA-B52 Antigen
  • Histocompatibility Antigens Class I / immunology*
  • Humans
  • Mice
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / immunology*
  • Phagocytosis / immunology
  • T-Lymphocytes / immunology*
  • Transgenes
  • Tumor Cells, Cultured

Substances

  • Antigens, Neoplasm
  • HLA-B Antigens
  • HLA-B52 Antigen
  • Histocompatibility Antigens Class I
  • MAGEA3 protein, human
  • Mageb3 protein, mouse
  • Neoplasm Proteins