In vivo gene transfer of a suicide gene under the transcriptional control of the carcinoembryonic antigen promoter results in bone marrow transduction but can avoid bone marrow suppression

We constructed the CEA419/CD retrovirus vector carrying the cytosine deamin ase (CD) gene directed by the carcinoembryonic antigen (CEA) promoter. pCD2 retrovirus vector carrying the CD gene directed by the retrovirus long ter minal repeat promoter was also used. When mice bearing intraperitoneally di sseminated colorectal carcinomas (CRCs) were infused intraperitoneally with pCD2 or CEA419/CD retrovirus-producing cells, a CD fragment was detected i n CRCs and bone marrow cells. It was shown that the CD gene was expressed b oth in CRCs and in the bone marrow of animals infused with pCD2 retrovirus- producing cells, while the CD gene was expressed solely in CRCs of animals infused with CEA419/CD retrovirus-producing cells. These results indicate t hat the use of a tumor-selective promoter may warrant the safety of in vivo gene therapy using suicide genes.