Adenoviral gene therapy of gastrointestinal tumour metastases in the liver

Summary

Gastrointestinal cancers are the second most common cause of cancer death. Once metastasised, 5 year survival is < 5% in gastrointestinal cancer. Because the liver is the preferred site for distant organ metastasis of colon cancer, treatment of hepatic metastases remains a challenge for experimental cancer therapy approaches. Gene therapy provides tools to combat cancer on a molecular level. In contrast to conventional chemotherapy, vectors are used to insert DNA into tumour cells, neighbouring parenchymal cells, or cells involved in the cellular immune defense. The shuttle vectors are of nonviral or viral origin. Adenoviral vectors have been developed for high efficiency in vivo gene transfer and expression. The incorporation of foreign DNA can result in direct tumour cell killing, using suicide genes. Cytokine genes, or genes encoding for tumour-specific antigens recognised by the cellular host immune system, can result in anti-tumoral immune stimulation. Experimental suicide-gene expression in hepatic metastasis of gastrointestinal tumours, utilising thymidine kinase and cytosine deaminase, results in significant tumour necrosis and regression. Intratumoral interleukin-2 and interleukin-12 gene expression can induce a systemic cellular antitumoral immune response, with long-term survival demonstrating the potential of this new therapeutic approach in cancer therapy.

Keywords:

• gene therapy
• adenoviral vectors
• suicide genes
• cytokine genes