TRANSPORT OF PEPTIDES TO EPIDERMAL LANDGERHANS CELLS

描述（由申请人提供）：更有效疫苗的一个关键是更好地将抗原递送到罕见的抗原呈递细胞，即树突状细胞。目前将疫苗注入树突状细胞的努力包括：a)昂贵的个体化离体程序，或b)激活带有炎症的先天免疫的佐剂，可能导致不可接受的毒性。我们的目标是开发一种简单、安全和廉价的局部疫苗递送系统，以表皮中的树突状细胞前体朗格汉斯细胞为目标。Lancell的方法是将抗原传递给大量朗格汉斯细胞，并诱导它们迁移到引流淋巴结，在那里它们可以激活初始T细胞。在I期研究中，我们开发了一种定量检测方法，该方法在朗格汉斯细胞迁移到皮肤引流淋巴结后，可直接测量与之相关的免疫原性肽。拟议的II期研究将优化我们的疫苗递送系统的每个参数，以在小鼠模型系统中诱导肿瘤免疫。

DESCRIPTION (provided by applicant): One key to more effective vaccines is better delivery of antigen to rare antigen-presenting cells, known as dendritic cells. Current efforts to deliver vaccines to dendritic cells entail: a) individualized ex vivo procedures that are costly, or b) adjuvants that activate innate immunity with inflammation that could result in unacceptable toxicity. Our goal is to develop a simple, safe and inexpensive, topical vaccine delivery system that targets dendritic cell precursors in the epidermis called Langerhans cells. Lancell's approach is to deliver antigen to large numbers of Langerhans cells and induce them to migrate to draining lymph nodes where they can activate naive T cells. In Phase I, we developed a quantitative assay that is sensitive and directly measures immunogenic peptides associated with Langerhans cells after their migration to skin draining lymph nodes. The proposed Phase II studies will optimize each parameter of our vaccine delivery system for the induction of tumor immunity in a murine model system. PROPOSED COMMERCIAL APPLICATION: Nearly 1.5 million new cases of cancer are diagnosed in the U.S. annually, and virtually all of these patients are candidates for an effective tumor immunotherapy. Tumor-associated antigens continue to be identified, but there is a need for more immunogenic vaccines. Lancell, L.L.C. is developing a vaccine delivery system exploiting epidermal Langerhans cells that is designed to be simple, potent and cost-effective.