Table 2.
This table summarizes the most important features of six main enzyme/prodrug systems that are used in GDEPT.
| Enzyme | Prodrug | Toxic Metabolite | Mechanism of Action | Bystander Effect | Distant Bystander Effect |
|---|---|---|---|---|---|
| Herpes Simplex Virus Thymidine Kinase | Ganciclovir (GCV) | Ganciclovir Triphosphate (GCV-TP) | Blocks DNA synthesis. S and G2 phase arrest. Mitochondrial damage. Active in dividing cells. |
High, when GJIC exists Low, when GJIC doesn’t exist |
Yes |
| Cytosine Deaminase | 5-Fluorocytosine (5-FC) | 5-Fluorouracil (5-FU) | Blocks DNA and RNA synthesis. Active mostly in dividing cells, but at high concentrations can inhibit growth of both dividing and non-dividing cells. |
High, independent of GJIC | Yes |
| Nitroreductase | CB1954 and analogues | 2-hydroxylamine and 4-hydroxylamine derivatives | DNA interstrand cross linker. Active in both dividing and non-dividing cells |
Very High, independent of GJIC | Yes |
| Carboxypeptidase G2 | CMDA; ZD-2767P | N-[4-[(2-Chloroethyl)(2- (mesyloxyethyl)amino)benzoic acid (CMBA); Bis-iodophenol mustard | DNA interstrand cross linker. Active in both dividing and non-dividing cells. |
High, independent of GJIC | Yes |
| Purine Nucleoside Phosphorylase | 6-methylpurine deoxyriboside | 6-methylpurine | Inhibits DNA, RNA and protein synthesis. Active in both dividing and non-dividing cells. |
High, independent of GJIC | Yes |
| Cytochrome P450 | Cyclophosphamide; Ifosfamide | phosphoramide mustard; acrolein | DNA interstrand crosslinking agent. Active mostly in dividing cells. |
Medium, independent of GJIC | Unknown |