Adenovirus-mediated suicide gene transfer to small cell lung carcinoma using a tumor-specific promoter.

The gastrin-releasing peptide (GRP) is expressed in most types of small cell lung carcinoma (SCLC) and the GRP promoter is thought to be potentially useful for tumor-specific expression of the suicide gene in SCLC. We constructed an adenovirus containing the herpes simplex thymidine kinase suicide gene driven by the GRP promoter (AdGRP-TK) and transfected it into GRP-expressing SCLC cells (SBC5) to confer sensitivity to ganciclovir (GCV). After infection with AdGRP-TK, SBC5 cells became more sensitive to GCV in vitro. In nude mice, a subcutaneously-inoculated tumor of SBC5 cells infected with AdGRP-TK in advance regressed completely after intraperitoneal administration of GCV. These results suggest that adenovirus-mediated gene transfer of the suicide gene followed by pro-drug treatment may be applicable to SCLC.