Evaluation of the therapeutic effect of replication-competent adenovirus on thyroid carcinomas

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We studied the therapeutic effect of the conditionally replication competent adenovirus on thyroid carcinomas in vitro and in vivo.(1) Differentiated thyroid carcinomas - We constructed the replicative adenovirus (AdTgE1A) in which the E1A gene, an indispensable gene for adenovirus replication, is placed downstream of thyroglobulin (Tg) promoter, a thyroid-specific promoter. Infection of AdTgElA led to E1A expression, virus replication (progeny production) and cytopathic effect in differentiated thyroid carcinoma cells expressing Tg, but not in other cells expressing no Tg. Furthermore, our studies demonstrated the enhanced effect of the combination of AdTgE1A and other gene therapies, including adenoviruses expressing a suicide gene or a cytokine.(2) Anaplastic thyroid carcinomas - To achieve p53-mutated cell-specific replication of adenovirus, we used "gene inactivation strategy" with p53-responseive promoter, Cre-LoxP system and double infection method. This strategy worked very well in vitro, but not so well in vivo, presumably because of low in vivo infectivity. Construction of a single adenovirus containing all the components was found impossible, since p53 promoter is not absolutely silent in 293 cells.