Gene Therapy: Development of Immunostimulatory Treatments for Cancer

Gene therapy encompasses a broad range of strategies, which aim to treat human diseases by the transfer of genetic infornlation. The idea was initially conceived for the treatment of inherited, monogenic disorders such as cystic fibrosis, in which the disease phenotype is due to the lack of a properly functional gene product in certain tissues. In principle, transfer of a functional gene encoding the relevant, wild-type protein could restore the affected cells to nonnality. It was soon realized that there are many other situations in which the introduction of specific genetic modifications to target cells could confer properties which could be of benefit in Jnany other clinical situations, including cardiovascular~neurological and infectious diseases, and cancer. There are numerous approaches to cancer gene therapy; the nlajority are designed to treat patients who have presented with cancer, rather than focusing on pre-emptive treatnlent of patients with known inherited predisposition to cancer. Approaches include interference with oncogene action within tumour cells; restoration of tumoursuppressor gene function; and expression of enzymes that enable the tumour cells to activate non-toxic prodrugs to cytotoxic species. This review focuses exclusively on cancer gene therapy strategies that are intended to induce immune responses against the malignant cells~ The approach is attractive, particularly because the disseminated nature of many cancers at later stages of the disease, and often at presentation, poses