Tumors Expressing the Cytosine Deaminase Suicide Gene Can Be Eliminated in Vivo with 5-Fluorocytosine and Induce Protective Immunity to Wild Type Tumor

摘要: Successful expression of the cytosine deaminase (CD) suicide gene in vivo is demonstrated three weakly immunogenic murine tumor models: 102 and 205 fibrosarcomas 38 adenocarcinoma. Normal mammalian cells do not contain deaminase, but transduced with retroviral vectors containing CD metabolize relatively nontoxic prodrug 5-fluorocytosine to highly toxic 5-fluorouracil. In vitro expressing are killed by while unmodified not. When injected into syngeneic mice, CD+ tumors can also be eliminated systemic treatment without significant toxicity host. Animals whose were resist subsequent rechallenge wild type tumor. This posttreatment immunity appears specific. Applications system therapy models discussed.