Development of cancer vaccines from fully synthetic mucin-based glycopeptide antigens. A vision on mucins from the bioorganic chemistry perspective - Carbohydrate Chemistry: Chemical and Biological Approaches - page 560

preparation to transgenic mice expressing human MUC1. After 35 days,
mice were challenged with Mouse Mammary Tumor cells. Robust MUC1
specific IgG antibody responses were detected and the obtained
antisera were able to significantly increase cancer cell lysis in two
MUC1-expressing tumor cell types. 61 Furthermore, cytotoxic T
lymphocytes (CTLs) were also induced and, strikingly, mice immunized
with the vaccine showed a significant reduction in tumor burden.
4 Conclusion
As illustrated by the examples presented in this chapter, there currently
exist powerful chemical methods for the synthesis of complex mucin-type
glycopeptides bearing truncated carbohydrate antigens that adequately
mimic the structure of tumor-associated mucins on the cell surface. In
addition, appropriate techniques have been developed for the ecient
coupling of these glycopeptide antigens to carrier proteins or immu-
nostimulating components, such as T-cell epitope peptides or Toll-like
receptor ligands, to afford the fully synthetic anti-tumor vaccines. The
development of these vaccines that closely mimic the nature of tumor cell
surface architecture and effectively activate T cells has been critical for
the successful generation of robust and reliable immune responses that
override the natural tolerance of the immune system. The immunological
and structural results showed herein with such vaccines indicate that
both the peptide and carbohydrate domains contribute to the distinctive
B-cell epitope, which causes the selective immune response. Importantly,
apart from serving as the antigenic determinant itself, the carbohydrate
seems to also exert a distinct conformational effect on the peptide
backbone, which, overall, is thought to play a key role in the immuno-
genicity and tumor selectivity of these mucin glycopeptide antigens. Fi-
nally, although great advances in the field have been made over the last
years, work in this direction is still in progress towards better and even
more e cient mucin-based synthetic vaccines. Currently, representative
examples are being evaluated in clinical trials with the ultimate goal of
developing clinically ecient vaccines to help patients fight against
cancers.
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