Introduction to the background, principles, and state of the art in suicide gene therapy.
Gene therapy is defined as a technology that aims to modify the genetic component of cells to gain therapeutic benefits. Suicide gene therapy (or gene-directed enzyme prodrug therapy [GDEPT]) is a two-step treatment for cancer (especially, solid tumors). In the first step, a gene for a foreign enzyme is delivered to the tumor by a vector. Following the expression of the foreign enzyme, a prodrug is administered during the second step, which is selectively activated in the tumor. This article discusses the principles and the theorectical background of GDEPT. A special emphasis is put on enzyme/prodrug systems developed for GDEPT, the design of prodrugs and the kinetic of their activation, the types and the mechanisms of bystander effect and its immunological implications. The possible strategies to improve GDEPT are also discussed.
Niculescu-Duvaz
Ion
I
Cancer Research, UK Centre for Cancer Therapeutics, Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey, SM2 5NG, UK.
Springer
Caroline J
CJ
D000818:Animals; D015195:Drug Design; D057487:Enzyme Therapy; D004798:Enzymes / Q000235:genetics*; D041722:Genes, Transgenic, Suicide / Q000235:genetics*; D015316:Genetic Therapy / Q000379:methods / Q000639:trends; D006801:Humans; D009369:Neoplasms / Q000235:genetics / Q000628:therapy*; D011355:Prodrugs / Q000627:therapeutic use
D004798:Enzymes; D011355:Prodrugs