Cytosine deaminase (CD) (CD)

Cytosine deaminase (CD) is an enzyme that catalyzes the hydrolytic deamination of cytosine to uracil (UniProt, 2024). In the context of the therapeutic candidate TMV-018, a "super cytosine deaminase" (SCD) is expressed by a recombinant, attenuated oncolytic measles virus (NCI Drug Dictionary). This enzyme is not naturally present in human cells, which allows it to serve as a key component in Gene-Directed Enzyme Prodrug Therapy (GDEPT) (ClinicalTrials.gov, NCT04195373). The SCD enzyme converts the non-toxic prodrug 5-fluorocytosine (5-FC) into the active chemotherapeutic agent 5-fluorouracil (5-FU) specifically within infected tumor cells (Patsnap Synapse). This localized production of 5-FU is intended to maximize anti-tumor efficacy while minimizing systemic toxicity (AdisInsight). TMV-018 has been investigated for the treatment of gastrointestinal cancers, including colorectal and gastric cancers, often in combination with immune checkpoint inhibitors (Taylor & Francis, 2021). Although clinical trials were initiated, some have been withdrawn due to recruitment challenges (ScanMedicine). The use of an oncolytic virus as a delivery vehicle further enhances the therapeutic effect by inducing immunogenic cell death and stimulating a systemic anti-tumor immune response (Cancers, 2020).

Other names

Super cytosine deaminaseSCDCytosine aminohydrolaseFCY1codA

Gene-Directed Enzyme Prodrug Therapy (GDEPT) involving the conversion of the non-toxic prodrug 5-fluorocytosine (5-FC) into the active cytotoxic agent 5-fluorouracil (5-FU) within tumor cells.