Nature Biotechnology
20, 64 - 69 (2002)
doi:10.1038/nbt0102-64
Induction of tumor-specific protective immunity by in situ Langerhans cell vaccineTadashi Kumamoto1, Eric K. Huang2, Hyun Joon Paek2, Akimichi Morita3, Hiroyuki Matsue1, Robert F. Valentini2
& Akira Takashima11
Department of Dermatology, University of Texas Southwestern Medical Center, Dallas, TX 75390. 2
Artificial Organs, Biomaterials, and Cellular Technology Program, Department of Molecular Pharmacology, Physiology, and Biotechnology, Brown University, Providence, RI 02912. 3
Department of Dermatology, Nagoya City University Medical School, Nagoya, Japan.
Correspondence should be addressed to Akira Takashima atakas@mednet.swmed.edu.Although anti-tumor immunity is inducible by dendritic cell (DC)−based vaccines, time- and cost-consuming "customizing" processes required for ex vivo DC manipulation have hindered broader clinical applications of this concept. Epidermal Langerhans cells (LCs) migrate to draining lymph nodes and undergo maturational changes on exposure to reactive haptens. We entrapped these migratory LCs by subcutaneous implantation of ethylene−vinyl−acetate (EVA) polymer rods releasing macrophage inflammatory protein (MIP)-3 (to create an artificial gradient of an LC-attracting chemokine) and topical application of hapten (to trigger LC emigration from epidermis). The entrapped LCs were antigen-loaded in situ by co-implantation of the second EVA rods releasing tumor-associated antigens (TAAs). Potent cytotoxic T-lymphocyte (CTL) activities and protective immunity against tumors were induced efficiently with each of three tested TAA preparations. Thus, tumor-specific immunity is inducible by the combination of LC entrapment and in situ LC loading technologies. Our new vaccine strategy requires no ex vivo DC manipulation and thus may provide time and cost savings.
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