Recent development in carbohydrate-based cancer vaccines

Abstract

Summary Tumor-associated carbohydrate antigens (TACAs) are important molecular markers on the cancer cell surface, useful for the development of therapeutic cancer vaccines or cancer immunotherapies. However, due to their poor immunogenicity and/or immunotolerance, most TACAs fail to induce T cell-mediated immunity that is critical for cancer therapy. This review summarizes the recent effort to overcome this problem via constructing TACA conjugates with improved immunogenicity, such as by covalently coupling TACAs to proper carrier molecules to form clustered or multi-epitopic conjugate vaccines, coupling TACAs to a T cell peptide epitope and/or an immunostimulant epitope to form fully synthetic multi-component glycoconjugate vaccines, and developing vaccines based on chemically modified TACAs, which is combined with metabolic engineering of cancer cells.

Automated Chemical Synthesis of Oligosaccharides and Glycoconjugates

“…The acquired knowledge was applied to a very effective synthesis of Globo-H hexasaccharide. This oligosaccharide is expressed on surfaces of different types of cancer cells, and this represents a key target for the development of anti cancer vaccines and therapeutics [24,27,[101][102][103][104][105]. The appreciation of the biological significance of Globo-H stimulated the interest in the synthetic community and the antigen has been synthesized by different methods [65,85,97,[106][107][108].…”

Glycodendrimers: versatile tools for nanotechnology

“…Carbohydrates are T-cell independent antigens since they are incompetent to trigger the participation of T-helper cells (Danishefsky, Allen, 2000;Roy, 2004;Becker et al, 2006;Liakatos, Kunz, 2007;Roy, 2008;Wilson et al, 2008;Guo, Boons, 2009;Guo, Wang, 2009;Westerlind, Kunz, 2011;Morelli, Poletti, Lay, 2011;Galan, Benito-Alifonso, Watt, 2011;Roy, Shiao, 2011). Consequently, they cannot induce immune cell proliferation, antibody class switch and affinity/specificity maturation on their own, as opposed to peptides and proteins that are T-cell dependent antigens.…”

“…stimulation of long lasting, high affinity antibodies, preferably of the IgG isotypes against the carbohydrate antigens. Several groups have developed systematic research projects aimed at the synthesis of various vaccine compositions (Livingston, 1995;Danishefsky, Allen, 2000;Kudryashov et al, 2001;Roy, 2004;Spohn et al, 2004;Freire et al, 2006;Liakatos, Kunz, 2007;Roy, 2008;Franco, 2008;Guo, Wang, 2009;Roy, Shiao, 2011). In spite of the limited success encountered with traditional vaccine formulations based on vaccine carriers harboring the above carbohydrate antigens (Koganty, Yalamati, Jiang, 2008), considerable efforts have been recently devoted to the chemical design of glycodendrimers.…”

The immunomodulating roles of glycoproteins in epithelial ovarian cancer

“…Clinical trials are currently underway to determine the efficacy of these T and Tn antigen based vaccination approaches. The inability of carbohydrate antigens to produce T cell responses is likely the cause of the lack of a robust clinical response in these T/Tn antigen based vaccination approaches (155). …”