SBIR-STTR Award

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.

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.

Thesaurus Terms:
Langerhans' cell, drug delivery system, peptide, protein transport, technology /technique development, tumor antigen, vaccine development antigenic peptide transporter, cell migration, transdermal drug delivery, vaccine flow cytometry, laboratory mouse, mass spectrometry