[cv]

Yeast-based Cancer Vaccine

Cancer immunotherapy is an emerging strategy to treat the industrialized world's second leading cause of death by mobilizing the immune system to recognize and attack tumor cells. Many promising studies and clinical trials have focused on dendritic cells as the key mediator of immunity. Dendritic cells are professional antigen-presenting cells that effectively uptake and process antigens, display antigenic peptides in the context of major histocompatibility complex molecules, and activate T cells in an antigen-specific manner. However, only mature, stimulated dendritic cells are capable of priming T cells to generate an immune response; immature dendritic cells may conversely elicit a state of tolerance for the antigen. In t his project, we propose to exploit recombinant yeast to load dendritic cells with a tumor-associated antigen. Dendritic cells readily phagocytose yeast cells, which have adjuvant properties. Using yeast surface display technology developed in this laboratory, we can further investigate the effects of modularly presenting various costimulatory factors on dendritic cell activation. In addition, we will isolate mutants of the tumor-associated antigen with improved expression/display properties that still retain the T cell epitopes.