Dedicated to Professor Steven V. Ley on the occasion of his 60th birthday A common feature of oncogenic transformed cells is the overexpression of oligosaccharides, such as Globo-H, Lewis Y , and Tn antigens. [1][2][3][4] Numerous studies have shown that this abnormal glycosylation can promote metastasis, [5] and hence its expression is strongly correlated with poor survival rates of cancer patients.
Several elegant studies have exploited the differential expression of tumor-associated carbohydrates for the development of cancer vaccines. [6,7] The inability of carbohydrates to activate helper T lymphocytes has complicated, however, their use as vaccines. [8] For most immunogens, including carbohydrates, the production of antibodies depends on the cooperative interaction of two types of lymphocytes, B cells and helper T cells. [9] Saccharides alone cannot activate helper T cells and therefore have a limited immunogenicity. The formation of low-affinity IgM antibodies and the absence of IgG antibodies manifest this limited immunogenicity.
To overcome the T cell independent properties of carbohydrates, past research has focused on the conjugation of saccharides to a foreign carrier protein (e.g. Keyhole Limpet Hemocyanin (KLH) or detoxified tetanus toxoid). [8,9] In this approach, the carrier protein enhances the presentation of the carbohydrate to the immune system and provides T epitopes (peptide fragments of 12-15 amino acids) that can activate helper T cells.
However, the conjugation of carbohydrates to a carrier protein poses several problems. In general, the conjugation chemistry is difficult to control, resulting in conjugates with ambiguities in composition and structure which may affect the reproducibility of an immune response. [10] Additionally, the foreign carrier protein can elicit a strong B cell response, which may lead to the suppression of an antibody response against the carbohydrate epitope. The latter is a greater