Prodrug-activating systems in suicide gene therapy

Prodrug-activating systems in suicide gene therapy.

Prodrug Activating Systems in Suicide Gene Therapy of Cancer: a Review

Theoretically, prodrugs are relatively noncytotoxic molecules, capable of being converted to cytotoxic species only at the site of the tumor, affording enhanced antitumor selectivity. One approach aimed at enhancing the selectivity of cancer chemotherapy for solid tumors relies on the application of prodrug-activating systems in suicide gene therapy. Enzyme-activating prodrug therapy, also know...

Prodrugs for Gene-Directed Enzyme-Prodrug Therapy (Suicide Gene Therapy)

This review focuses on the prodrugs used in suicide gene therapy. These prodrugs need to satisfy a number of criteria. They must be efficient and selective substrates for the activating enzyme, and be metabolized to potent cytotoxins preferably able to kill cells at all stages of the cell cycle. Both prodrugs and their activated species should have good distributive properties, so that the resu...

Methioninase cancer gene therapy with selenomethionine as suicide prodrug substrate.

In this study, we report a novel approach to gene-directed enzyme prodrug therapy for cancer. This gene therapy strategy exploits the toxic pro-oxidant property of methylselenol, which is released from selenomethionine (SeMET) by cancer cells with the adenoviral-delivered methionine alpha,gamma-lyase (MET) gene cloned from Pseudomonas putida. In MET-transduced tumor cells, the cytotoxicity of S...

Attenuated Salmonella targets prodrug activating enzyme carboxypeptidase G2 to mouse melanoma and human breast and colon carcinomas for effective suicide gene therapy.

PURPOSE We engineered the oncolytic Salmonella typhimurium-derived bacterium VNP20009 as a vector to target delivery to tumors of the prodrug-activating enzyme carboxypeptidase G2 (CPG2) and to show enhanced antitumor efficacy on administration of different prodrugs. EXPERIMENTAL DESIGN We characterized CPG2 expression in vectors by immunoblotting, immunofluorescence, and enzyme activity. We ...