Immunome Research
Open Access

Disaccharide mimics as drugs against cancer and epitopes for anti-cancer vaccine candidates

2^nd International Conference on Antibodies and Therapeutics

July 11-12, 2016 Philadelphia, USA

Pierre Vogel and Loay K Awad

Swiss Institute of Technology in Lausanne, Switzerland

Posters & Accepted Abstracts: Immunome Res

Abstract :

Cancer associated mucin glycoprotein MUC1 is characterized by the presence of altered carbohydrates such as Tn (�?�?�?±-Nacetylgalactosamine), sTn (sialyl-1-6-Tn) and the Thomsen-Friedenreich (TF: �?�?�?²-D-Galp-1-3-�?�?�?±-D-GalNAcp) antigen (tumor associated carbohydrate antigens: TACAs) that are conjugated to proteins via O-�?�?�?±-galactosylation of serine or/and threonine. Patients immunized with synthetic TF conjugated with KLH (keyhole limpet hemocyanin) + QS21 adjuvant can generate IgM and IgG antibodies. Because the disaccharide TF is hydrolyzed rapidly in the body, strong immune response requires longer lived disaccharides. Fluorinated TACAs have been proposed which elicit IgG antibodies found to cross-react with native TF epitopes. We have found that a C-linked disaccharide analogue constructed from �?�?�?²-D-Galp-1-CH2-3-�?�?�?±-D-GalNAcp (applying Danishesky�?¢�?�?�?�?s method for the conjugation with KLH+QS21 adjuvant induces a strong immune response in mice. Interestingly, much weaker immune response was observed with a stereoisomeric antigen constructed from the �?�?�?±-C-galactoside analogue of TF disaccharide (�?�?�?±-D-Galp-1-CH2- 3-�?�?�?±-D-GalNAc-O-Ser. Several strategies and methods have been developed for the synthesis of C-linked disaccharides including disaccharide mimics incorporating iminosugars C-linked to sugars and sugar mimics such as conduritols and cyclitols. The latter work was motivated by the search for specific glycosidase and glycosyltransferase inhibitors that are potential drugs against cancers and other diseases.

Biography :

Email: pierre.vogel@epfl.ch