HUMAN LUNG-CARCINOMA CELLS ENGINEERED TO RELEASE IL2, IL7, GM-CSF ANDTNF-ALPHA - GROWTH IN NU NU MICE AND MODULATION OF TGF-BETA(1) PRODUCTION/

A human lung adenocarcinoma cell line (LC89) was transduced with the I L2, IL7, GM-CSF and TNF alpha genes by retroviral vector mediated infe ction. This induced the constitutive and stable release of all cytokin es. No difference or modulation was found in the parental and gene tra nsduced LC89 cells with regard to cytokine receptor expression, in vit ro cell growth and proliferation, nor in cell surface expression of di fferent adhesion molecules. Following injection into immunosuppressed nu/nu mice, IL2 gene transduced LC89 cells lost their tumorigenic pote ntial. LC89 cells engineered to release IL7 and TNF alpha grew in nu/n u mice, but in 40% of the animals tumor regression was observed. GM-CS F gene transduced LC89 cells showed a tumorigenic capacity identical t o that of the parental clone. The levels of TGF beta(1) released by IL 2, IL7 and GM-CSF gene transduced LC89 cells were markedly reduced com pared to those of the parental and TNF alpha gene transduced cells. Th e results of this study support the concept that human lung cancer cel ls engineered with different cytokine genes maintain their intrinsic m orphologic and proliferative features, while their tumorigenic and imm unosuppressive capacities can be profoundly down-modulated. Both these effects are optimally achieved following insertion of the IL2 gene, s uggesting that vaccination protocols with IL2 gene transduced tumor ce lls may be considered for the management of human lung cancer.