Principles of mucin structure: Implications for the rational design of cancer vaccines derived from MUC1-glycopeptides

Abstract

Cancer is currently one of the world's most serious public health problems. Significant efforts are being made to develop new strategies that can eradicate tumours selectively without detrimental effects to healthy cells. One promising approach is focused on the design of vaccines that contain partially glycosylated mucins in their formulation. Although some of these vaccines are in clinical trials, a lack of knowledge about the molecular basis that governs the antigen presentation, and the interactions between antigens and the elicited antibodies has limited their success thus far. This review focuses on the most significant milestones achieved to date in the conformational analysis of tumour-associated MUC1 derivatives both in solution and bound to antibodies. The effect that the carbohydrate scaffold has on the peptide backbone structure and the role of the sugar in molecular recognition by antibodies are emphasised. The outcomes summarised in this review may be a useful guide to develop new antigens for the design of cancer vaccines in the near future.