Bacterial cytosine deaminase (bCD) (bCD)

Bacterial cytosine deaminase (bCD) is an enzyme, typically derived from Escherichia coli (codA gene), that is not naturally expressed in human cells (PubMed: 10637062). In adenoviral gene therapy, an adenovirus vector delivers the bCD gene to tumor cells, a strategy known as Gene-Directed Enzyme Prodrug Therapy (GDEPT) (NCBI: NBK6230). The primary function of bCD in this context is to catalyze the deamination of the non-toxic prodrug 5-fluorocytosine (5-FC) into the potent cytotoxic agent 5-fluorouracil (5-FU) (PubChem: CID 3366). This localized conversion leads to high intratumoral concentrations of 5-FU, which inhibits thymidylate synthase and incorporates into RNA and DNA, causing cell death (PubMed: 17072310). Because 5-FU can diffuse across cell membranes, it exerts a 'bystander effect,' killing nearby non-transduced cancer cells (Journal of Gene Medicine: 10.1002/jgm.952). This approach is primarily utilized in treating solid tumors, such as prostate cancer and glioblastoma, to enhance the therapeutic index of chemotherapy (ClinicalTrials.gov: NCT00583453). Safety considerations include the potential for systemic 5-FU toxicity and the host's inflammatory response to the adenoviral delivery vehicle.

Other names

codACytosine aminohydrolaseAd-CDE. coli cytosine deaminaseBacterial CD

The enzyme catalyzes the hydrolytic deamination of the non-toxic prodrug 5-fluorocytosine (5-FC) into the potent chemotherapeutic agent 5-fluorouracil (5-FU). 5-FU subsequently undergoes intracellular conversion by host enzymes into active metabolites, such as 5-FdUMP, which inhibits thymidylate synthase, and 5-FUTP, which incorporates into RNA, ultimately leading to cell cycle arrest and apoptosis (PubMed: 17072310).