Gene therapy in cancer via use of a retrovector having a tumor specificity and expressing inducible nitric oxide synthase.
The generation of retrovectors (retroviral vectors) with tumor specificity is a promising and effective approach to targeted gene therapy of cancer. Carcinoembryonic antigen (CEA), overexpressed by various tumor cells, provides a specific tool for tumor-specific targeting by retrovectors. The conventional suicidal gene delivery systems need additional drugs other than their gene products. The inducible nitric oxide synthase (iNOS) gene product yields nitric oxide (NO), which directly induces autocytotoxicity and cytolysis of bystander cells. A novel method is described here that explains how to prepare a novel recombinant retrovector that displays a chimeric envelope protein containing a single-chain fragment variable (scFv) antibody to CEA and carries the iNOS gene in the genome. The resultant bifunctional retrovector showed a specific delivery of the iNOS gene to human CEA-expressing carcinoma cells, resulting in the direct and efficient killing of CEA-expressing carcinoma cells by induction of apoptosis. This approach may offer a one-step procedure for effective gene therapy of CEA-expressing tumors and also be applied to other tumor antigens expressed on cancer cells.
Kuroki
Masahide
M
Department of Biochemistry, Fukuoka University School of Medicine, Japan.
D000818:Animals; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D002277:Carcinoma / Q000235:genetics* / Q000628:therapy; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D007128:Immunoglobulin Fragments / Q000276:immunology; D009369:Neoplasms / Q000235:genetics* / Q000628:therapy; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000235:genetics* / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D012190:Retroviridae / Q000235:genetics*; D014407:Tumor Cells, Cultured
D002272:Carcinoembryonic Antigen; D007128:Immunoglobulin Fragments; D009569:Nitric Oxide; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II