Due to changes in
glycosyltransferase expression during
oncogenesis, the
glycoproteins of
cancer cells often carry highly truncated
carbohydrate chains compared to those on healthy cells. These
glycans are known as
tumor-associated carbohydrate antigens (TACAs), and are prime targets for use in
vaccines for the prevention and treatment of
cancer. Herein, we review the state-of-the-art in targeting the immune system toward
tumor-associated
glycopeptide antigens via synthetic self-adjuvanting
vaccines, in which the antigenic and adjuvanting moieties of the
vaccines are present in the same molecule. The majority of the self-adjuvanting
glycopeptide cancer vaccines reported to date employ
antigens from
mucin 1, a
protein which is highly over-expressed and aberrantly glycosylated in many forms of
cancer. The adjuvants used in these
vaccines predominantly include
lipopeptide- or lipoamino
acid-based TLR2 agonists, although studies investigating stimulation of TLR9 and TLR4 are also discussed. Many of these adjuvants are highly lipophilic, and, upon conjugation to antigenic
peptides, provide amphiphilic
vaccine molecules. The amphiphilic nature of these
vaccine constructs can lead to the formation of higher-order structures by
vaccines in
solution, which are likely to be important for their efficacy in vivo.