Chapter 24: Tumour-associated glycopeptide antigens and their modification in anticancer vaccines
Published:20 Mar 2014
S. Hartmann, B. Palitzsch, M. Glaffig, and H. Kunz, in Carbohydrate Chemistry: Chemical and Biological Approaches, Volume 40, ed. A. Pilar Rauter, T. Lindhorst, and Y. Queneau, The Royal Society of Chemistry, 2014, vol. 40, ch. 24, pp. 506-532.
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Glycopeptide antigens are obtained by solid-phase glycopeptide synthesis using fluorenylmethoxycarbonyl-(Fmoc)-protected O-glycosyl threonine and serine building blocks representing the tumour-associated mucin carbohydrate antigens. Conjugation of the synthetic mucin glycopeptide antigens with T-cell epitope peptides and/or immune stimulating lipopeptides affords fully synthetic two- and three-component vaccines useful for immunization of mice. Conjugates of the synthetic tumour-associated glycopeptide antigens with carrier proteins, in particular with tetanus toxoid, proved to be potent antitumour vaccines inducing high titres of IgG antibodies, which strongly bind to breast tumour cells. Mimics of the carbohydrate antigens within these glycopeptides also result in efficient vaccines as long as the carbohydrate structure remains closely related to the natural tumour-associated carbohydrate antigen.