TRANSPORT OF PEPTIDES TO EPIDERMAL LANGERHANS CELLS

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A major factor limiting the efficacy of vaccines is the failure to target the critical antigen-presenting cells. Current efforts to target vaccines to dendritic cells use individualized ex vivo procedures that are too costly for widespread use. Our goal is to develop a cost-effective, topical method to deliver antigenic peptides to epidermal Langerhans cells. Topical delivery of antigen to epidermal Langerhans cells with concomitant induction of Langerhans cell migration is a potent inducer of immunity. We have identified two potential means for active transdermal transport of tumor- associated peptides. In this Phase I proposal, we plan to 1) develop quantitative assays for transport of a prototypic murine tumor-associated antigenic peptide to Langerhans cells. Using' these assays, we will 2) determine the most efficient procedure for transdermal transport of peptide to epidermal Langerhans cells. If the amount' of peptide associated with Langerhans cells that have migrated to the draining lymph node is within the range need to activate primary T cells, we will have established the feasibility of this approach for tumor immunotherapy. PROPOSED COMMERCIAL APPLICATIONS: Nearly 1.5 million new cases of cancer are diagnosed in the U.S. annually; virtually all of these patients are candidates for an 'effective tumor immunotherapy. Tumor-associated antigenic peptides are currently being identified, but there is a need for better peptide vaccine delivery systems. We propose to develop a topical peptide delivery system exploiting epidermal Langerhans cells that would be simple and cost-effective.