Tri-component MUC1 glycopeptide vaccine induced both humoral and cellular immune responses in MUC1.Tg mice with MMT tumor

Effective immunotherapy for cancer depends on both cellular and humoral immune responses to tumor antigens. MUC1, which is expressed at increased levels on breast cancer, also exhibits altered glycosylation that contributes to the formation of novel antigens. The identification of MHC class I and II binding peptides derived from tumor-associated MUC1 has facilitated the development of MUC1 based cancer vaccines. We have shown that the MHC class I binding epitopes from MUC1 tandem repeat, when given as emulsification with adjuvants, has always resulted in strong cellular response with no antibody response. It is possible that better immunogenicity would be obtained using glycopeptides more representative of the novel forms of MUC1 as seen in cancer to which individuals may be less tolerant and that direct linking of the vaccine components would result in a superior immune response than delivering them as a mix. Here we show that a three-component vaccine composed of a TLR2 agonist, a helper epitope and a T cell epitope, which is also a B cell epitope, derived from the MUC1 can break tolerance and elicit both humoral and cellular immune responses. Immunization with the MUC1 glycopeptide vaccine led to a significant reduction in tumor burden compared to mice treated with adjuvants only and empty liposomes. The tri-component vaccine activated MUC1 glycopeptide-specific cytotoxic CD8+ T cells and elicited robust titers of IgG antibodies that lyse relevant tumor cells by ADCC.