Cytosine deaminase (microbial) (CD)

Microbial cytosine deaminase (CD) is an enzyme derived from bacteria or fungi, such as Saccharomyces cerevisiae, that is not naturally expressed in human cells (Source: UniProt P25334). It plays a vital role in the pyrimidine salvage pathway by catalyzing the deamination of cytosine into uracil. In the field of oncology, this enzyme is utilized as a suicide gene in Gene-Directed Enzyme Prodrug Therapy (GDEPT). When expressed by a viral vector like TMV-018 (an oncolytic measles virus also known as MV-FCU1), the enzyme converts the non-toxic antifungal prodrug 5-fluorocytosine (5-FC) into the potent chemotherapeutic agent 5-fluorouracil (5-FU) directly within the tumor (Source: PubMed 25653123). This localized conversion allows for high intratumoral concentrations of 5-FU, which inhibits DNA synthesis and induces apoptosis in cancer cells while minimizing the systemic toxicities typically associated with intravenous 5-FU administration (Source: PubMed 11595580). Furthermore, the 5-FU produced can diffuse into neighboring non-infected cells, creating a bystander effect that enhances the overall anti-tumor efficacy. TMV-018 is specifically designed to treat advanced solid tumors by combining the direct oncolytic properties of the measles virus with the targeted cytotoxic action of the cytosine deaminase enzyme (Source: ClinicalTrials.gov NCT04101331).

Other names

Yeast cytosine deaminaseyCDFCU1Cytosine aminohydrolaseMicrobial cytosine deaminaseMV-FCU1

The enzyme catalyzes the conversion of the non-toxic prodrug 5-fluorocytosine (5-FC) into the potent cytotoxic agent 5-fluorouracil (5-FU) within the tumor microenvironment, leading to localized cell death and a bystander effect.