Gene-based cancer vaccines:: an ex vivo approach

The application of gene transfer techniques to immunotherapy has animated the field of gene-based cancer vaccine research. Gene transfer strategies were developed to bring about active immunization against tumor-associated antigens (TAA) through gene transfer technology. A wide variety of viral and nonviral gene transfer methods have been investigated for immunotherapeutic purposes. Ex vivo strategies include gene delivery into tumor cells and into cellular components of the immune system, including cytotoxic T cells and dendritic cells (DC). The nature of the transferred genetic material as well as the gene transfer method has varied widely depending on the application. Several of these approaches have already been translated into clinical gene therapy trials. In this review, we will focus on the rationale and types of ex vivo gene-based immunotherapy of cancer. Critical areas for future development of gene-based cancer vaccines are addressed, with particular emphasis on use of DC and on the danger-tolerance hypothesis. Finally, the use of gene-modified DC for tumor vaccination and its prospects are discussed.