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[Cancer Research 54, 1503-1506, March 15, 1994]
© 1994 American Association for Cancer Research
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Tumors Expressing the Cytosine Deaminase Suicide Gene Can Be Eliminated in Vivo with 5-Fluorocytosine and Induce Protective Immunity to Wild Type Tumor

Craig A. Mullen1, Melissa M. Coale, Robert Lowe and R. Michael Blaese

Metabolism Branch, Division of Cancer Biology, Diagnosis and Centers, National Cancer Institute, NIH, Bethesda, Maryland 20892

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

1 To whom requests for reprints should be addressed, at Metabolism Branch, Division of Cancer Biology, Diagnosis and Centers, National Cancer Institute, NIH, Bldg. 10, Room 4N115, Bethesda, MD 20892.

Received 10/21/93. Accepted 1/18/94.




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HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
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Copyright © 1994 by the American Association for Cancer Research.