Cytosine deaminase-uracil phosphoribosyltransferase fusion protein (sCD) (sCD)

Cytosine deaminase-uracil phosphoribosyltransferase fusion protein (sCD) is an engineered enzyme used in gene-directed enzyme prodrug therapy (GDEPT), primarily for the treatment of high-grade gliomas and other solid tumors (PubMed: 27103014). It is a chimeric protein combining the activities of yeast-derived cytosine deaminase (yCD) and uracil phosphoribosyltransferase (yUPRT), which work synergistically to convert the non-toxic antifungal prodrug 5-fluorocytosine (5-FC) into the potent chemotherapeutic 5-fluorouracil (5-FU) and subsequently into 5-fluorouridine monophosphate (5-FUMP) (UniProt: P05016, P25334). The term 'Super CD' is also used to describe specific optimized variants, such as the D92E mutant of yeast cytosine deaminase, which exhibits enhanced catalytic efficiency and thermostability (PubMed: 16132040). In clinical applications, the sCD gene is typically delivered to tumor cells via a viral vector, such as the retroviral replicating vector Vocimagene amiretrorepvec (Toca 511). Once expressed, the enzyme creates a localized 'chemotherapy factory' within the tumor, where the produced 5-FU can diffuse to neighboring non-transduced cells to exert a 'bystander effect' (PubMed: 21974805). This approach aims to maximize anti-tumor efficacy while minimizing the systemic side effects typically associated with intravenous 5-FU administration.

Other names

Super cytosine deaminasesCDyCD-yUPRTFCY1-FUR1 fusion proteinVocimagene amiretrorepvec transgene productYeast cytosine deaminase (D92E mutant)

The enzyme converts the non-toxic prodrug 5-fluorocytosine (5-FC) into the cytotoxic metabolite 5-fluorouracil (5-FU), which is then further converted to 5-fluorouridine monophosphate (5-FUMP) to inhibit DNA and RNA synthesis.