Construction and characterization of a recombinant adenovirus directing expression of the MAGE-1 tumor-specific antigen.
The finding that many human melanomas express distinct antigens that can be recognised by specific cytolytic T lymphocytes (CTL) implies that immunotherapeutic strategies against this cancer might prove effective. The ex vivo delivery of a tumour-associated antigen to autologous cells and the subsequent re-administration of these cells to the patient might prove effective in boosting the T cell immune response. Recombinant human adenoviral vectors provide an efficient delivery system and have many advantages over other viral and non-viral delivery vehicles. Infection of a panel of human melanoma cell lines by AdCMVMAGE-1, a novel recombinant adenovirus which incorporates the full-length MAGE-1 cDNA, was shown to induce production of high levels of MAGE-1 protein. Incubation of transduced HLA-A1 expressing melanoma cell lines with 2 anti-MAGE-1.A1 CTL clones resulted in specific recognition and lysis of target cells, indicating that the exogenous MAGE-1 protein was processed and presented in a normal manner. Furthermore, quantitative analyses demonstrated a correlation between the efficiency of transduction and the proportion of cells lysed. Importantly for future clinical trials, stimulation of peripheral blood lymphocytes (PBLs) from a melanoma patient by AdCMVMAGE-1-transduced autologous cells resulted in the generation of specific CTLs against the MAGE-1 antigen. Together, our data emphasize the utility of adenoviruses as vaccination vehicles and highlight the potential efficacy of this approach for the treatment of melanoma.
Reed
D S
DS
Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Epalinges, Switzerland.
Romero
P
P
Rimoldi
D
D
Cerottini
J C
JC
Schaack
J
J
Jongeneel
C V
CV
D000256:Adenoviridae / Q000235:genetics*; D000951:Antigens, Neoplasm / Q000096:biosynthesis*; D003602:Cytotoxicity, Immunologic; D005822:Genetic Vectors; D006801:Humans; D008545:Melanoma / Q000276:immunology*; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D011995:Recombination, Genetic; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014162:Transfection / Q000379:methods; D014407:Tumor Cells, Cultured; D001616:beta-Galactosidase / Q000096:biosynthesis
D000951:Antigens, Neoplasm; C072011:MAGEA1 protein, human; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins; D011993:Recombinant Fusion Proteins; D001616:beta-Galactosidase