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

The recent identification of the sequences of the peptides derived from a number of human melanomaassociated 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 HLAA1-positive patients with melanoma expressing the MAGE-1 antigen.This work was supported by a PHS grant CA 61398 and in part by the Lavery Cancer Research Fund