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 be molecularly modified by particle-mediated gene transfer with a "gene gun", using genes for interferon-gamma (IFN-gamma), the B7-1 costimulatory molecule (CD80), and human leukocyte antigen (HLA)-A2, to augment expression of both HLA molecules and B7-1. Established and early passage melanoma cells transfected with human IFN-gamma complementary DNA (cDNA) produced IFN-gamma (50-5,000 pg/mL). The biological effect of this IFN-gamma transgene included an upregulation, or de novo appearance, of HLA expression. These melanoma cells had no detectable baseline surface expression of the B7-1 costimulatory molecule, but 8% to 31% of these cells became B7-1 positive with no selection procedure after 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 expressed both HLA-DR and B7-1. In combination gene transfer experiments with 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 HLA and B7-1 can be achieved by particle-mediated gene delivery and presents a promising strategy to stimulate antimelanoma T-cell immunity. Key words: Melanoma; T cells; B7-1 costimulatory molecule (CD80); major histocompatibility complex.
Albertini
M R
MR
University of Wisconsin Comprehensive Cancer Center, Madison, USA.
Emler
C A
CA
Schell
K
K
Tans
K J
KJ
King
D M
DM
Sheehy
M J
MJ
D018122:B7-1 Antigen / Q000096:biosynthesis* / Q000235:genetics; D019470:Biolistics; D002460:Cell Line; D018076:DNA, Complementary; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D015870:Gene Expression; D017930:Genes, Reporter; D015316:Genetic Therapy / Q000379:methods; D006680:HLA Antigens / Q000096:biosynthesis*; D015789:HLA-A2 Antigen / Q000096:biosynthesis; D006684:HLA-DR Antigens / Q000096:biosynthesis; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000235:genetics; D008285:Major Histocompatibility Complex; D008545:Melanoma / Q000628:therapy; D010957:Plasmids; D011994:Recombinant Proteins / Q000096:biosynthesis; D014162:Transfection / Q000379:methods*; D014407:Tumor Cells, Cultured; D001616:beta-Galactosidase / Q000096:biosynthesis
D018122:B7-1 Antigen; D018076:DNA, Complementary; D006680:HLA Antigens; D015789:HLA-A2 Antigen; D006684:HLA-DR Antigens; D011994:Recombinant Proteins; D007371:Interferon-gamma; D001616:beta-Galactosidase