Targeted adenoviral vectors for cancer gene therapy (Review)

Abstract

In order to realise the full potential of gene therapy as a rational approach to the treatment of cancer, it will be necessary to achieve delivery of the therapeutic gene selectively to target tumour cells. Such cancer cell-specific gene delivery is mandated in the context of locoregional or compartmentalised carcinomas, and is also an absolute requirement for the treatment of disseminated disease. Moreover, underlying any cancer gene therapy approach is the need to achieve a high level of efficiency of gene transfer to the target cells. Of the existing viral and nonviral gene delivery vehicles, the adenoviral vector uniquely fulfils two requirements of an intravenously administered vector for cancer gene therapy: systemic stability and the ability to accomplish efficient transduction of cancer cells. However, it is necessary to modify native adenoviral tropism in order to achieve selective transduction of target tumour cells. A number of strategies have been developed for this purpose, involving genetic or immunological modifications to either of two adenoviral capsid proteins, the fibre and penton base. These strategies are designed to generate a targetable, injectable vector which would represent a major advance in the field of cancer gene therapy.