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Gene Therapy for Carcinoembryonic Antigen-producing Human Lung Cancer Cells by Cell Type-specific Expression of Herpes Simplex Virus Thymidine Kinase Gene¹

Department of Medicine III, Osaka University Medical School, 2-2, Yamadaoka, Suita, Osaka 565 [T. O., Y. T., I. T., S. H., T. Ku., I. K., T. Ki.], and Suntory Institute for Biomedical Research, 1-1-1, Wakayamadai, Shimamoto-cho, Mishima-gun, Osaka 618 [S. O.], Japan

A carcinoembryonic antigen (CEA)-producing human lung cancer cell line (A549), a nonproducing human lung cancer cell line (CADO-LC9), and a human uterine cervical cancer (HeLa) were transfected with the herpes simplex virus thymidine kinase (HSV-TK) gene regulated by 445 nucleotides upstream from the translational start of CEA gene. Fifty % growth inhibitory concentration of ganciclovir (GCV) was 0.57 µM for HSV-TK-transfected A549; relative sensitivity to GCV was more than 1000 times higher compared to the 50% growth inhibitory concentration of the parental cell line. Both CADO-LC9 and HeLa transfected with HSV-TK were still resistant to GCV. There was no difference in either morphology or doubling time between HSV-TK-transfected and parental clones. Injections (i.p.) of GCV resulted in significant regression of HSV-TK-transfected A549 tumors in nude mice. These data show the possibility of gene therapy using the cell type-specific promoter of CEA gene against CEA-producing adenocarcinoma of the lung.

¹ Supported in part by Grants-in-Aid for Cancer Research from the Ministry of Health and Welfare and from the Ministry of Education, Science, and Culture in Japan.

² To whom requests for reprints should be addressed.

Received 7/18/94. Accepted 9/ 1/94.

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