Presentation of synthetic peptide antigen encoded by the MAGE-1 gene by granulocyte/macrophage-colony-stimulating-factor-cultured macrophages from HLA-A1 melanoma patients

Cancer Immunol Immunother. 1995 Apr;40(4):268-71. doi: 10.1007/BF01519901.

Abstract

The recent identification of the sequences of the peptides derived from a number of human melanoma-associated antigens has presented opportunities for developing a specific-peptide-based vaccine in this form of cancer. Since antigen-presenting cells (APC) play a crucial role in the induction of the T-cell-mediated immune response, we examined whether or not ex vivo cultured APC, bearing the appropriate MHC restricting elements, when pulsed with a relevant melanoma-specific cytotoxic-T-lymphocyte (CTL)-determined peptide, can present the peptide to the CTL. Here we show that a population of cells, derived from the monocyte/macrophage lineage from peripheral blood and grown in granulocyte/macrophage-colony-stimulating factor, exhibit many essential characteristics of "professional" APC (dendritic-type morphology with a proportion of the population, the B7 molecule, and high levels of MHC class I and class II molecules, CD11b and CD54 molecules) and are capable of efficiently presenting the nonapeptide, EADPTGHSY, encoded by the melanoma antigen MAGE-1 gene, to the MAGE-1-specific CTL clone, 82/30. These results suggest that this type of autologous ex vivo cultured population of professional APC, when pulsed with the relevant-CTL-determined peptide, can serve as a novel type of candidate vaccine for active specific immunization against HLA-A1-positive patients with melanoma expressing the MAGE-1 antigen.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Antigen-Presenting Cells / cytology
  • Antigen-Presenting Cells / immunology
  • Antigen-Presenting Cells / metabolism*
  • Antigens, Neoplasm / biosynthesis*
  • Antigens, Neoplasm / genetics*
  • Base Sequence
  • Cells, Cultured
  • Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology*
  • Histocompatibility Antigens Class I / metabolism
  • Humans
  • Lymphocyte Activation / immunology
  • Macrophages / cytology
  • Macrophages / drug effects*
  • Macrophages / metabolism*
  • Melanoma / blood*
  • Melanoma / immunology
  • Melanoma-Specific Antigens
  • Molecular Sequence Data
  • Neoplasm Proteins*
  • Stimulation, Chemical
  • T-Lymphocytes / immunology
  • T-Lymphocytes, Cytotoxic / immunology
  • Tumor Cells, Cultured

Substances

  • Antigens, Neoplasm
  • Histocompatibility Antigens Class I
  • MAGEA1 protein, human
  • Melanoma-Specific Antigens
  • Neoplasm Proteins
  • Granulocyte-Macrophage Colony-Stimulating Factor