ICROS · Cancer associated glycan epitopes via Ionic Catch and Release Oligosaccharide Synthesis (ICROS)

The quest for an effective cancer vaccine was initiated over 100 years ago from the moment vaccines against infectious diseases were successfully applied, and despite the many advances to date, the search for therapeutic vaccines derived from carbohydrate antigens is still an ongoing challenge. Carbohydrate antigens of tumour cells are uniquely effective targets for antibody-mediated active and passive cancer immunotherapy and have also proven to be effective targets for immune recognition and attack. The gastrointestinal tract posses a protective epithelial barrier as part of the basic innate protective system, which produces a secreted mucus layer that contains hundreds of different mucin type O-linked oligosaccharides known to be connected with diseases such as breast and colon cancers. However, little is known about the specific role of this family of oligosaccharides in disease due to the lack of tools for study. Access to structurally defined complex carbohydrates is still a very laborious process and combinatorial approaches to prepare diverse libraries of oligosaccharides remain limited. A general automated method for oligosaccharide assembly will allow rapid preparation of structures of interest. This programme’s long term aim is to develop carbohydrate-based cancer vaccines that elicit both a strong humoral- and cellular immune response against colon and breast cancers. To achieve our objectives, we plan to apply a novel and improved methodology (ICROS) to the synthesis of mucin type carbohydrate fragments, which are otherwise not available, ready to be immobilized onto nanocarrier systems for initial biological (antibody screening) and immunogenic assays. The understanding of these glycosylation patterns at both molecular and functional level will help us identify mucin oligosaccharide based antigens that will pave the way to the development of target specific anti cancer vaccines.