DUAL EXPRESSION OF HUMAN-LEUKOCYTE ANTIGEN MOLECULES AND THE B7-1 COSTIMULATORY MOLECULE (CD80) ON HUMAN-MELANOMA CELLS AFTER PARTICLE-MEDIATED GENE-TRANSFER

The aim of this study was to determine if human melanoma cells could b e molecularly modified by particle-mediated gene transfer with a ''gen e gun'', using genes for interferon-gamma (IFN-gamma), the B7-1 costim ulatory molecule (CD80), and human leukocyte antigen (HLA)-A2, to augm ent expression of both HLA molecules and B7-1. Established and early p assage melanoma cells transfected with human IFN-gamma complementary D NA (cDNA) produced IFN-gamma (50-5,000 pg/mL). The biological effect o f this IFN-gamma transgene included an upregulation, or de novo appear ance, of HLA expression. These melanoma cells had no detectable baseli ne surface expression of the B7-1 costimulatory molecule, but 8% to 31 % of these cells became B7-1 positive with no selection procedure afte r gene transfer with human B7-1 cDNA. After combination gene transfer with cDNAs for both IFN-gamma and B7-1, 9% to 33% of these cells expre ssed both HLA-DR and B7-1. In combination gene transfer experiments wi th cDNAs for both HLA-A2 and B7-1, dual expression of HLA-A2 and B7-1 was achieved in 10% to 17% of the melanoma cells. Thus, the molecular modification of human melanoma cells to increase expression of both HL A and B7-1 can be achieved by particle-mediated gene delivery and pres ents a promising strategy to stimulate antimelanoma T-cell immunity.