Mucin 1 (MUC1) is a transmembrane glycoprotein that is highly overexpressed in a range of epithelial tumours. During cancer initiation and development, aberrant expression of glycosyltransferases leads to expression of tumour-associated carbohydrate antigens (TACAs) on MUC1, which are absent from healthy cells. Humoral immune responses to TACA-containing MUC1 have been correlated with inscreased surivival in cancer patients. For these reasons, MUC1 has been ranked 2nd out of 75 of the most promising cancer antigens for cancer vaccine development. Our laboratory has designed and synthesised novel cancer vaccine candidates comprising the TLR 2 agonists Pam3Cys, Pam2Cys, and macrophage-activating lipopeptide 2 (MALP2) as adjuvants covalently attached to MUC1 glycopeptides. These vaccines were constructed in an iterative manner, combining three different MUC1 peptides (unglycosylated or containing 2 different TACAs) with a MALP2 peptide fragment and Pam2Cys to generate the fully synthetic vaccines.
When injected into C57BL/6 mice, the resulting self-adjuvanting vaccine constructs were shown to induce high titres of class-switched antibodies capable of recognising tumour-associated MUC1 glycoforms. Importantly, this response occurred in the absence of any external adjuvant or helper T cell epitope. The presence of such antibodies is likely to be important for the control of cancer grometastasis and residual disease. The CD8+ and CD4+ T cell responses to the vaccine candidates were also analysed through both in vivo and in vitro methods.
In summary, three novel MUC1-MALP2 self-adjuvanting cancer vaccine candidates will be presented. These vaccine candidates induced robust humoral immune responses despite the lack of external adjuvants or helper T cell epitopes.