The overarching goal of our research is to develop cancer immunotherapeutics that target tumor-associated-carbohydrate-antigens (TACAs) found on malignant cells. In the process of carcinogenesis, certain glycosyltransferases are over-expressed, which leads to different glycosylation patterns than those of normal cells. For example, the Thomsennouveau (Tn) antigen is expressed abundantly in human breast, ovarian and colon cancers. These abnormal glycosylations on tumor cell surfaces provide significant opportunities for researchers to develop carbohydrate-based anticancer therapeutics. The strategy used for most carbohydrate-based cancer vaccines entails immunogenic proteins as carriers to cross over into the cellular arm of the immune system because of the inherent T-cell independent nature of TACSs. There are both advantages and disadvantages of this strategy. We have been working with the unique zwitterionic capsular polysaccharide PS A1 to find alternative pathways avoiding protein carriers and at same time retain both a cellular and humoral immune response. PS A1 is found on Bacteroides fragilis’ cell wall, consisting of a tetrasaccharide-core repeating unit carrying an electrostatic charge character on adjacent monosaccharides able to induce a specific and selective immune response similar to that noted for exogenous proteins. This lecture will describe the synthesis of Tn-PS A1 conjugates and their application in developing mAbs to further understand glycoimmunology.
Originally published at chemistry.nd.edu.