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提呈细胞，即树突状细胞。目前向树突状细胞提供疫苗的努力包括：a)昂贵的个体化体外程序，或b)激活先天免疫的佐剂，其炎症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，该系统针对表皮中的树突状细胞前体细胞，称为朗格汉斯细胞。Lancell的方法是将抗原传递给大量的朗格汉斯细胞，并诱导它们迁移到引流的淋巴结，在那里它们可以激活原始T细胞。在第一阶段，我们开发了一种灵敏的定量分析方法，可以直接测量朗格汉斯细胞迁移到皮肤引流淋巴结后与其相关的免疫原肽。拟议的第二阶段研究将优化我们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。 建议的商业应用： 在美国，每年有近150万新确诊的癌症病例，几乎所有这些患者都是有效的肿瘤免疫疗法的候选者。肿瘤相关抗原继续被识别，但需要更多的免疫原性疫苗。Lancell，L.L.C.正在开发一种利用表皮朗格汉斯细胞的疫苗递送系统，该系统设计简单、有效且具有成本效益。

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.