Interleukin-2 gene transduction into freshly isolated lung adenocarcinoma cells with adenoviral vectors.
We evaluated the efficiency of gene transduction and of gene expression by adenoviral vectors in human lung adenocarcinoma cells. Freshly isolated cancer cells were collected from pleural effusions in adenocarcinoma patients by centrifugation with a Percoll gradient. Adenoviral vectors 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 vector with a regulatory sequence of chicken beta-actin as promoter and an enhancer derived from cytomegalovirus produced a higher transduction ratio and greater expression levels than adenoviral vectors with other promoter systems. Transduction with Adex1CA vectors containing the human interleukin-2 (IL-2) gene (Adex1CAhIL-2) resulted in enhanced secretion of IL-2 from gene-modified lung cancer cells. Treatment with normal human serum inhibited gene transduction by Adex1CAhIL-2 but did not inhibit gene expression after transduction by Adex1CAhIL-2. The secretion of IL-2 from the gene-modified cells, which were irradiated at 100 Gy before transduction, continued for 8 days. In a mouse model, the intrapleural injection of IL-2 gene-modified 3LL cells transduced by Adex1CAhIL-2 could cure the pre-existing lung tumours with malignant pleural effusions to induce tumor-specific immunity. But these therapies did not show any therapeutic benefit on the pre-existing tumor in subcutaneous region. These data suggest a potentially useful but limited clinical role of Adex1CAhIL-2 in gene therapy for lung cancer patients.
Heike
Y
Y
Pharmacology Division, National Cancer Center Research Institute, Tokyo, Japan.
Takahashi
M
M
Kanegae
Y
Y
Sato
Y
Y
Saito
I
I
Saijo
N
N
D000256:Adenoviridae / Q000378:metabolism*; D000818:Animals; D003470:Culture Media / Q000737:chemistry / Q000494:pharmacology; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D018014:Gene Transfer Techniques; D017930:Genes, Reporter / Q000235:genetics; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D007114:Immunization; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009374:Neoplasms, Experimental / Q000628:therapy*; D014407:Tumor Cells, Cultured; D001616:beta-Galactosidase / Q000378:metabolism
D003470:Culture Media; D007376:Interleukin-2; D001616:beta-Galactosidase