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Enhanced Efficacy of Transcriptionally Targeted Suicide Gene/Prodrug Therapy for Thyroid Carcinoma with the Cre-loxP System

Departments of Pharmacology 1 [Y. N., M. N.] and Nature Medicine [E. N., H. N., S. Y.], Nagasaki University School of Medicine, Nagasaki 852-8523, and Department of Internal Medicine 4, Saitama Medical College, Saitama, 350-0495 [M. I.], Japan

Our recent study demonstrates the feasibility of the thyroglobulin (TG) promoter in transcriptionally targeted gene therapy for thyroid carcinomas expressing TG, albeit less effectively than the constitutive viral promoter. The present study was, therefore, designed to enhance the activity of the TG promoter with the Cre-loxP system. Our data demonstrate that the in vitrocytotoxic effect of herpes simplex virus thymidine kinase/ganciclovir obtained with the TG promoter and the Cre-loxP system is 5–10-fold higher than that with the TG promoter alone. Enhanced tumor growth inhibition was also observed in in vivotumor models. These data indicate the usefulness of the Cre-loxP system to enhance the activity of a tissue (or tumor)-specific promoter in transcriptionally targeted cancer gene therapy.

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