INTERLEUKIN-2 GENE TRANSDUCTION INTO FRESHLY ISOLATED LUNG ADENOCARCINOMA CELLS WITH ADENOVIRAL VECTORS

We evaluated the efficiency of gene transduction and of gene expressio n by adenoviral vectors in human lung adenocarcinoma cells, Freshly is olated cancer cells were collected from pleural effusions in adenocarc inoma patients by centrifugation with a Percoll gradient, Adenoviral v ectors resulted in effective gene transduction into human lung cancer cell lines and into freshly isolated lung adenocarcinoma cells, In an experiment using the beta-galactosidase (LacZ) gene, the Adex1CA vecto r with a regulatory sequence of chicken beta-actin as promoter and an enhancer derived from cytomegalovirus produced a higher transduction r atio and greater expression levels than adenoviral vectors with other promoter systems, Transduction with Adex1CA vectors containing the hum an interleukin-2 (IL-2) gene (Adex1CAhIL-2) resulted in enhanced secre tion of IL-2 from gene-modified lung cancer cells, Treatment with norm al human serum inhibited gene transduction by Adex1CAhIL-2 but did not inhibit gene expression after transduction by Adex1CAhIL-2. The secre tion of IL-2 from the gene-modified cells, which were irradiated at 10 0 Gy before transduction, continued for 8 days, In a mouse model, the intrapleural injection of IL-2 gene-modified 3LL cells transduced by A dex1CAhIL-2 could cure the pre-existing lung tumors with malignant ple ural effusions to induce tumor-specific immunity. But these therapies did not show any therapeutic benefit on the pre-existing tumor in subc utaneous region. These data suggest a potentially useful but limited c linical role of Adex1CAhIL-2 in gene therapy for lung cancer patients.