Nature Medicine
2, 1122 - 1128 (1996)
doi:10.1038/nm1096-1122
DNA−based immunization by in vivo transfection of dendritic cellsCal Condon1, Simon C. Watkins2, Christina M. Celluzzi1, Kathleen Thompson1
& Louis D. Falo Jr.1, 3
1Department of Dermatology,the University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, 190 Lothrop Street, Pittsburgh, Pennsylvania 15213, USA e-mail: Lof2@pitt.edu
2Department of Cell Biology and Physiology, and the University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, 190 Lothrop Street, Pittsburgh, Pennsylvania 15213, USA Delivery of antigen in a manner that induces effective, antigen−specific immunity is a critical challenge in vaccine design. Optimal antigen presentation is mediated by professional antigen−presenting cells (APCs) capable of taking up, processing and presenting antigen to T cells in the context of costimulatory signals required for T−cell activation. Developing immunization strategies to optimize antigen presentation by dendritic cells, the most potent APCs, is a rational approach to vaccine design. Here we show that cutaneous genetic immunization with naked DNA results in potent, antigen−specific, cytotoxic T lymphocyte−mediated protective tumor immunity. This method of immunization results in the transfection of skin−derived dendritic cells, which localize in the draining lymph nodes. These observations provide a basis for further development of DNA−based vaccines and demonstrate the feasibility of genetically engineering dendritic cells in vivo.
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