Head and neck cancer: gene therapy approaches. Part 1: adenoviral vectors

Treatment options for recurrent or refractory head and neck cancer are limited. The goal of gene therapy is to introduce new genetic material into cancer cells without affecting toxicity to surrounding malignant cells. The most common vehicles for delivery of genes are adenoviruses. Adenoviruses gain access to malignant and normal cell cytoplasm via viral ligand binding to a unique cell surface receptor (the coxsackie adenovirus receptor [CAR]). However, this receptor is not cancer specific. Genetic modification of adenoviral DNA can create cancer specific targeting. Adenoviruses can be modified to express cancer specific ligands thereby focusing binding to malignant tissue. Furthermore, adenoviral delivered genes can be put under cancer specific promoter control to further limit gene expression in malignant tissue. Increased antitumour activity from such modifications has been demonstrated preclinically and several clinical trials have been completed demonstrating safety and clinical activity of non-replicating and conditional replicating adenoviral vector thereby opening the door for gene delivery and cancer specific targeting.