TY - JOUR
T1 - Human lung carcinoma cells engineered to release IL2, IL7, GM-CSF and TNFα
T2 - Growth in nu/nu mice and modulation of TGFβ1 production
AU - Guarini, Anna
AU - Riera, Ludovica
AU - Reato, Gigliola
AU - Carbone, Anna
AU - Cignetti, Alessandro
AU - Gilliotos, Anna
AU - Lanfrancone, Luisa
AU - Melani, Cecilia
AU - Paul, Ralph W.
AU - Forni, Guido
AU - Foa, Robin
PY - 1996/4
Y1 - 1996/4
N2 - A human lung adenocarcinoma cell line (LC89) was transduced with the IL2, IL7, GM-CSF and TNFα genes by retroviral vector mediated infection. This induced the constitutive and stable release of all cytokines. No difference or modulation was found in the parental and gene transduced LC89 cells with regard to cytokine receptor expression, in vitro cell growth and proliferation, nor in cell surface expression of different adhesion molecules. Following injection into immunosuppressed nu/nu mice, IL2 gene transduced LC89 cells lost their tumorigenic potential. LC89 cells engineered to release IL7 and TNFα grew in nu/nu mice, but in 40% of the animals tumor regression was observed. GM-CSF gene transduced LC89 cells showed a tumorigenic capacity identical to that of the parental clone. The levels of TGFβ1 released by IL2, IL7 and GM-CSF gene transduced LC89 cells were markedly reduced compared to those of the parental and TNFα gene transduced cells. The results of this study support the concept that human lung cancer cells engineered with different cytokine genes maintain their intrinsic morphologic and proliferative features, while their tumorigenic and immunosuppressive capacities can be profoundly down-modulated. Both these effects are optimally achieved following insertion of the IL2 gene, suggesting that vaccination protocols with IL2 gene transduced tumor cells may be considered for the management of human lung cancer.
AB - A human lung adenocarcinoma cell line (LC89) was transduced with the IL2, IL7, GM-CSF and TNFα genes by retroviral vector mediated infection. This induced the constitutive and stable release of all cytokines. No difference or modulation was found in the parental and gene transduced LC89 cells with regard to cytokine receptor expression, in vitro cell growth and proliferation, nor in cell surface expression of different adhesion molecules. Following injection into immunosuppressed nu/nu mice, IL2 gene transduced LC89 cells lost their tumorigenic potential. LC89 cells engineered to release IL7 and TNFα grew in nu/nu mice, but in 40% of the animals tumor regression was observed. GM-CSF gene transduced LC89 cells showed a tumorigenic capacity identical to that of the parental clone. The levels of TGFβ1 released by IL2, IL7 and GM-CSF gene transduced LC89 cells were markedly reduced compared to those of the parental and TNFα gene transduced cells. The results of this study support the concept that human lung cancer cells engineered with different cytokine genes maintain their intrinsic morphologic and proliferative features, while their tumorigenic and immunosuppressive capacities can be profoundly down-modulated. Both these effects are optimally achieved following insertion of the IL2 gene, suggesting that vaccination protocols with IL2 gene transduced tumor cells may be considered for the management of human lung cancer.
KW - Cytokines
KW - Gene transfer
KW - GM-CSF
KW - IL2
KW - IL7
KW - Lung cancer
KW - TGFβ
KW - TNFα
UR - http://www.scopus.com/inward/record.url?scp=17144465456&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=17144465456&partnerID=8YFLogxK
M3 - Article
AN - SCOPUS:17144465456
VL - 8
SP - 765
EP - 772
JO - International Journal of Oncology
JF - International Journal of Oncology
SN - 1019-6439
IS - 4
ER -