mesenchymal stem cells transduced with cytosine deaminase

Mesenchymal stem cells transduced with cytosine deaminase (MSC/CD) is an experimental cell-based gene therapy designed to provide targeted delivery of chemotherapy to tumor sites. In this system, mesenchymal stem cells (MSCs)—often allogeneic and chosen for their innate ability to home to tumors and injured tissues—are genetically engineered, typically via retroviral or lentiviral vectors, to express the bacterial enzyme cytosine deaminase (CD). This construct utilizes a "suicide gene" approach: when the non-toxic prodrug 5-fluorocytosine (5-FC) is administered systemically, the CD enzyme within the MSC cellular vehicle converts it locally into the potent cytotoxic agent 5-fluorouracil (5-FU). This localized conversion creates high concentrations of 5-FU within the tumor microenvironment, inducing apoptosis in neighboring cancer cells through the inhibition of thymidylate synthase and disruption of DNA/RNA synthesis (the bystander effect), while minimizing systemic toxicity. This therapy is primarily being investigated for the treatment of high-grade gliomas, such as glioblastoma multiforme (GBM), as well as other solid tumors including gastric cancer and osteosarcoma.

Other names

MSC-CDcytosine deaminase-expressing mesenchymal stem cellsCD-transduced MSCsallogeneic mesenchymal stem cells transduced with cytosine deaminaseallogeneic MSC/CD