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Combination Therapy With Suicide and Cytokine Genes for Hepatic Metastases of Lung Cancer

Yok-Lam Kwong; Shu-Hsia Chen; Ken Kosai; Milton Finegold; Savio L. C. Woo
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Affiliations: From the Howard Hughes Medical Institute, Baylor College of Medicine, Houston, Texas,  From the Department of Cell Biology, Baylor College of Medicine, Houston, Texas,  From the Department of Pathology, Baylor College of Medicine, Houston, Texas,  From the Howard Hughes Medical Institute; and the Department of Cell Biology, Baylor College of Medicine, Houston, Texas

Affiliations: From the Howard Hughes Medical Institute, Baylor College of Medicine, Houston, Texas,  From the Department of Cell Biology, Baylor College of Medicine, Houston, Texas,  From the Department of Pathology, Baylor College of Medicine, Houston, Texas,  From the Howard Hughes Medical Institute; and the Department of Cell Biology, Baylor College of Medicine, Houston, Texas

Affiliations: From the Howard Hughes Medical Institute, Baylor College of Medicine, Houston, Texas,  From the Department of Cell Biology, Baylor College of Medicine, Houston, Texas,  From the Department of Pathology, Baylor College of Medicine, Houston, Texas,  From the Howard Hughes Medical Institute; and the Department of Cell Biology, Baylor College of Medicine, Houston, Texas

Affiliations: From the Howard Hughes Medical Institute, Baylor College of Medicine, Houston, Texas,  From the Department of Cell Biology, Baylor College of Medicine, Houston, Texas,  From the Department of Pathology, Baylor College of Medicine, Houston, Texas,  From the Howard Hughes Medical Institute; and the Department of Cell Biology, Baylor College of Medicine, Houston, Texas


1997 by the American College of Chest Physicians


Chest. 1997;112(5):1332-1337. doi:10.1378/chest.112.5.1332
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Abstract

Metastases of lung cancer are a major cause of treatment failure. To evaluate the therapeutic efficacy of gene therapy in metastatic lung cancer, we used adenoviral (ADV) mediated transfer of the herpes simplex virus thymidine kinase (HSV-tk) gene and the cytokine gene interleukin-2 (IL-2) to treat a murine model of metastatic lung cancer in the liver. Hepatic metastases were established by intrahepatic implantation of LL2 cells in syngeneic recipient mice. One week after tumor implantation, various replication defective ADV vectors were injected intratumorally. Treatment with a vector expressing the HSV-tk followed by ganciclovir administration with ADV.tk resulted in significant regression of tumor (p<0.01) as well as prolongation of survival (p<0.001). While a vector expressing mouse IL-2 ADV.IL-2 alone was ineffective, combination therapy with HSV-tk resulted in further tumor regression and improvement of animal survival (p<0.05). These results demonstrate that suicide and cytokine genes can be utilized in combination to treat metastatic lung cancer in vivo.


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