Induction of protective immunity against syngeneic rat cancer cells by expression of the cytosine deaminase suicide gene

The use of the cytosine deaminase (CD)/5-fluorocytosine suicide system as a cancer gene therapy approach enables selective killing of CD-modified cell s as well as the ablation of non-modified tumor cells due to a bystander ef fect that has been suggested to involve the immune system in vivo. Using a stable CD transfectant of the tumorigenic rat adenocarcinoma cell line AS ( AS/CD), an antitumoral response against the CD expressing cell line as well as the parental cell line could be induced by stepwise vaccinations in syn geneic animals. AS/CD tumor regression occurred independently of 5-fluorocy tosine treatment and was sufficient to protect 37% of the animals against s ubsequent challenge with tumorigenic doses of the parental AS cell line. Im mune rats contained lymphocytes able to specifically lyse CD modified as we ll as unmodified AS tumor cells in vitro, most likely contributing to the i n vivo antitumoral reaction. Thus, the CD suicide system seems to be suitab le not only for a local tumor gene therapy but also for the application as therapy of metastatic tumors and minimal residual disease.