DNA and RNA modified dendritic cell vaccines

The purpose of this paper is to describe the strategies for genetic modification of dendritic cells for use in active immunotherapy for the treatment of malignancies. An accruing body of data supports the concept of directing a therapeutic immune response, mediated by the cellular arm of the immune system, against cancers in vivo. Dendritic cells are the most potent inducers of T cell-mediated immune responses against tumor-expressed antigens, by virtue of their ability to present tumor antigens in the context of major histocompatibility molecules to naïve T cells with receptors specific for the antigen. A variety of methods for directing antigens to the MHC molecules of dendritic cells and augmenting their T cell stimulatory activity have been developed. This paper describes one group of promising strategies, the genetic modification of dendritic cells to direct the expression of tumor antigens, costimulatory molecules, and stimulatory cytokines. Genetic modification can be effected by either DNA or RNA, and the genetic material may be delivered by vectors or by physical means. These approaches are now entering human clinical trials.