Adenovirus-mediated gene delivery to dendritic cells

Dendritic cells (DCs) are "professional" antigen-presenting cells (APCs) that are uniquely capable of activating and instructing a naive immune system to mount a specific cellular and humoral response. Recognition of this crucial function makes the development of technologies for DC-based immuno-therapies a priority for the treatment of a wide variety of diseases. The most immediate impact of this emerging technology will be in the treatment of cancer and the development of third generation vaccines to protect against viral and intracellular pathogens. In addition to elicitation of immune responses, DCs also function to maintain tolerance to "self." Once the biological basis for this important function is understood, future applications of DC-based immuotherapies may be developed to ameliorate autoimmune diseases or enhance acceptance of transplanted organs. The feasibility of "engineering" the function of DCs has been realized by recent advances in ex vivo methodologies that allow selective DC propagation, antigen loading, and genetic modification in vitro for subsequent therapeutic transfer into the host. Ultimately, the ability to genetically modify these cells will allow us to design DC-mediated interventions that will direct predictable control of either immune activation or tolerance in vivo.