PMID: 20127041Feb 4, 2010Paper

Combination gene therapy of lung cancer with conditionally replicating adenovirus and adenovirus-herpes simplex virus thymidine kinase

International Journal of Molecular Medicine
Jin Young OhChoon-Taek Lee

Abstract

A major obstacle to the success of gene therapy strategies that directly target cancer cells is the low gene transfer rate. To address this problem, we had previously proposed a combination adenoviral gene therapy containing a conditionally replicating adenovirus (CRAD) expressing mutant E1 (Delta24RGD), and a replication-defective E1-deleted adenovirus to enhance the efficiency of gene transfer. Suicide/pro-drug gene therapy has an important additional benefit to the therapy of cancer. This relates to the transfer and expression of non-mammalian genes encoding enzymes that convert non-toxic pro-drugs into cellular toxins. We investigated the interaction between CRAD (Delta24RGD) and a replication-defective E1-deleted adenovirus (ad-HSTK) containing a suicide gene (HSTK: herpes simplex virus thymidine kinase gene) with respect to therapeutic gene production and tumor cell killing efficacy. Combined transduction of CRAD and ad-HSTK increased the transduction efficiency of HSTK and increased its sensitivity to ganciclovir (GCV) more efficiently than ad-HSTK alone. Transfer of medium of CRAD and ad-HSTK co-transduced cells induced the transfer of HSTK (media transferable bystander effect), and enhanced its sensitivity to GCV. In a...Continue Reading

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