Gene-based cancer vaccines: an ex vivo approach

The application of gene transfer techniques to immunotherapy has animated t he field of gene-based cancer vaccine research. Gene transfer strategies we re developed to bring about active immunization against tumor-associated an tigens (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 in to cellular components of the immune system, including cytotoxic T cells an d dendritic cells (DC). The nature of the transferred genetic material as w ell as the gene transfer method has varied widely depending on the applicat ion. Several of these approaches have already been translated into clinical gene therapy trials. In this review, we will focus on the rationale and ty pes of ex vivo gene-based immunotherapy of cancer. Critical areas for futur e 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 discuss ed.