Synthesis of oligosaccharides and glycoconjugates to develop anti-cancer vaccines

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The basic expertise of our research group resides in synthetic carbohydrate chemistry. The main goal of research program is to design through chemical synthesis safe anti-cancer vaccines based on Tumor Associated Carbohydrates Antigens (TACAs). Our research program targets the antigens: dimericLex, LeaLex, Ley, LebLea and LeyLex (KH-1). We aim at discovering fragments of dimericLex and LeaLex that are able to trigger safe immune responses targeted against colorectal cancer cells and squamous lung carcinoma cells, respectively. We also aim at increasing the ability of the TACAs to trigger an efficient (T-cell dependent) immune response by investigating a new class of molecules made of the Ley antigen linked to a zwitterionic polysaccharide (PS A1). PS A1 is extracted from Bacteroides fragilis and has been shown to elicit the desired immune response without the need for an adjuvant or carrier protein. Given our expertise, we are also designing efficient synthetic strategies to prepare the more challenging heptasaccharides: LebLea and LeyLex (KH-1) which are both associated with adenocarcinomas. Because it has been well-established that cancer cells express several different TACAs at levels that vary over the course of cellular development, we will use these two antigens to investigate the preparation of divalent tetanus toxoid conjugates via amide bond formation and copper-free click chemistry.