TARGETED ADENOVIRAL VECTORS FOR CANCER GENE-THERAPY (REVIEW)

In order to realise the full potential of gene therapy as a rational a pproach to the treatment of cancer, it will be necessary to achieve de livery of the therapeutic gene selectively to target tumour cells. Suc h cancer cell-specific gene delivery is mandated in the context of loc oregional or compartmentalised carcinomas, and is also an absolute req uirement for the treatment of disseminated disease. Moreover, underlyi ng any cancer gene therapy approach is the need to achieve a high leve l of efficiency of gene transfer to the target cells. Of the existing viral and nonviral gene delivery vehicles, the adenoviral vector uniqu ely fulfils two requirements of an intravenously administered vector f or cancer gene therapy: systemic stability and the ability to accompli sh efficient transduction of cancer cells. However, it is necessary to modify native adenoviral tropism in order to achieve selective transd uction of target tumour cells. A number of strategies have been develo ped for this purpose, involving genetic or immunological modifications to either of two adenoviral capsid proteins, the fibre and penton bas e. These strategies are designed to generate a targetable, injectable vector which would represent a major advance in the field of cancer ge ne therapy.