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 fro m a number of human melanoma-associated antigens has presented opportu nities for developing a specific-peptide-based vaccine in this form of cancer. Since antigen-presenting cells (APC) play a crucial role in t he induction of the T-cell-mediated immune response, we examined wheth er or not ex vivo cultured APC, bearing the appropriate MHC restrictin g 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/m acrophage lineage from peripheral blood and grown in granulocyte/macro phage-colony-stimulating factor, exhibit many essential characteristic s of ''professional'' APC (dendritic-type morphology with a proportion of the population, the B7 molecule, and high levels of MHC class I an d class II molecules, CD11b and CD54 molecules) and are capable of eff iciently presenting the nonapeptide, EADPTGHSY, encoded by the melanom a antigen MAGE-1 gene, to the MAGE-1-specific CTL clone, 82/30. These results suggest that this type of autologous ex vivo cultured populati on of professional APC, when pulsed with the relevant-CTL-determined p eptide, can serve as a novel type of candidate vaccine for active spec ific immunization against HLA-A1-positive patients with melanoma expre ssing the MAGE-1 antigen.