PMID: 11912516Mar 26, 2002Paper

Midkine promoter-based adenoviral suicide gene therapy to midkine-positive pediatric tumor

Journal of Pediatric Surgery
Yasuo AdachiP N Reynolds

Abstract

Suicide gene therapy based on the delivery of the herpes simplex virus thymidine kinase gene combined with ganciclovir (HSV-tk/GCV) is a promising approach for cancer treatment. Adenoviral (Ad) vectors are useful gene delivery vehicles for this approach; however, because these agents possess a high natural tropism for the liver, systems must be designed to avoid potential hepatotoxicity induced by expression of the therapeutic gene in this organ. It has been reported that Wilms' tumors or neuroblastomas express a high level of midkine (MK), a heparin-binding growth factor. In addition, no MK expression is observed in mouse or human liver. The authors investigated the application of MK promoter-based adenoviral gene therapy for MK-positive tumors, especially Wilms' tumors or neuroblastomas, and have shown that the MK promoter retains its fidelity in the adenoviral context, having low activity in liver and high activity in MK-positive tumor cells. We present herein the efficacy of in vivo tumor regression as well as prevention of lethal hepatic toxicity by using the MK promoter in an Ad vector-based HSV-tk/GCV treatment approach. Ad vectors, AdMKTK or AdCMVTK, encoding HSV-tk under the control of the MK or cytomegalovirus promote...Continue Reading

Citations

Sep 16, 2004·The Journal of Gene Medicine·Daniel T ReinDavid T Curiel

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