Prodrug-activating bacterial enzyme

Prodrug-activating bacterial enzymes represent a functional class of non-human proteins utilized in site-specific cancer therapies, including Gene-Directed Enzyme Prodrug Therapy (GDEPT) and Antibody-Directed Enzyme Prodrug Therapy (ADEPT) [1, 5]. These enzymes, such as cytosine deaminase (CD), nitroreductase (NTR), and carboxypeptidase G2 (CPG2), are delivered to tumor sites where they catalyze the conversion of systemically administered, non-toxic prodrugs into potent cytotoxic agents [1, 2]. This localized activation significantly increases the therapeutic index of chemotherapy by concentrating the active drug within the tumor microenvironment while minimizing systemic exposure [1, 5]. A hallmark of this approach is the "bystander effect," where the activated drug diffuses from the enzyme-expressing cells to kill neighboring non-expressing tumor cells, thereby overcoming the limitations of heterogeneous gene delivery [9]. Despite their therapeutic potential, challenges include the inherent immunogenicity of bacterial proteins and the requirement for highly selective delivery systems to prevent off-target activation in healthy tissues [1, 5].

Other names

Microbial prodrug-activating enzymeSuicide gene enzymeGDEPT enzymeADEPT enzymeBacterial prodrug-activating enzyme

Enzymatic conversion of a non-toxic prodrug into a cytotoxic active drug