Immunogenicity of a Fully Synthetic MUC1 Glycopeptide Antitumor Vaccine Enhanced by Poly(I:C) as a TLR3‐Activating Adjuvant

Fully synthetic MUC1 glycopeptide antitumor vaccines have a precisely specified structure and induce a targeted immune response without suppression of the immune response when using an immunogenic carrier protein. However, tumor‐associated aberrantly glycosylated MUC1 glycopeptides are endogenous structures, “self‐antigens”, that exhibit only low immunogenicity. To overcome this obstacle, a fully synthetic MUC1 glycopeptide antitumor vaccine was combined with poly(inosinic acid:cytidylic acid), poly(I:C), as a structurally defined Toll‐like receptor 3 (TLR3)‐activating adjuvant. This vaccine preparation elicited extraordinary titers of IgG antibodies which strongly bound human breast cancer cells expressing tumor‐associated MUC1. Beside the humoral response, the poly(I:C) glycopeptide vaccine induced a pro‐inflammatory environment, very important to overcome the immune‐suppressive mechanisms, and elicited a strong cellular immune response crucial for tumor elimination. Do you see what I:C? A synthetic vaccine consisting of a tumor‐associated MUC1 glycopeptide (red) and a polio virus T‐cell epitope (green) supported by poly(I:C) as a synthetic adjuvant was found to induce a dramatically strong, tumor‐cell‐recognizing immune response including complement‐activating IgG subtypes. Antitumor‐effective cytokines and cytotoxic T‐cells were also induced by this fully synthetic vaccine formulation.