In this study, we determined the in vitro and in vivo efficacy of
sodium iodide symporter (NIS) gene transfer and the therapeutic potential of
oncolytic virotherapy combined with radioiodine
therapy using a conditionally replicating oncolytic adenovirus. For this purpose, we used a replication-selective adenovirus in which the E1a gene is driven by the mouse
alpha-fetoprotein (AFP) promoter and the human NIS gene is inserted in the E3 region (Ad5-E1/AFP-E3/NIS). Human
hepatocellular carcinoma cells (HuH7) infected with Ad5-E1/AFP-E3/NIS concentrated radioiodine at a level that was sufficiently high for a
therapeutic effect in vitro. In vivo experiments demonstrated that 3 days after intratumoral (i.t.) injection of Ad5-E1/AFP-E3/NIS HuH7 xenograft
tumors accumulated approximately 25% ID g(-1) (percentage of the injected dose per gram
tumor tissue) (123)I as shown by (123)I
gamma camera imaging. A single i.t. injection of Ad5-E1/AFP-E3/NIS (virotherapy) resulted in a significant reduction of
tumor growth and prolonged survival, as compared with injection of saline. Combination of
oncolytic virotherapy with radioiodine treatment (radiovirotherapy) led to an additional reduction of
tumor growth that resulted in markedly improved survival as compared with virotherapy alone. In conclusion, local in vivo NIS gene transfer using a replication-selective oncolytic adenovirus is able to induce a significant
therapeutic effect, which can be enhanced by additional (131)I application.