Reduced breast tumor growth after immunization with a tumor-restricted MUC1 glycopeptide conjugated to tetanus toxoid.

Preventive vaccination against tumor-associated endogenous antigens is considered to be an attractive strategy for the induction of a curative immune response concomitant with a long-lasting iininirtiologic memory, The union MUC1 is a promising tumor antigen, as its tumor-associated form differs from the glycoprotein form expressed on healthy cells Due to aberrant glycosylation in tumor cells, the specific peptide epitopes in its backbone are accessible and can be bound by antibodies induced by vaccination, Breast cancer patients develop per se only low levels of T cells and antibodies recognizing tumor-associated MUCL and clinical trials with tumor-associated MUC1 yielded unsatisfactory therapeutic effects, indicating an urgent need to improve humoral immunity against this tumor entity. Herein, we demonstrate that preventive vaccination against tumor-associated human MUC1 results in a specific humoral immune response, a slowdown of tumor progression and an increase in survival of breast tumor-bearing mice, For preventive vaccination, we used a synthetic vaccine containing a tumor-associated glycopeptide structure of human MUC1 coupled to Tetanus Toxoid. The glycopeptide consists of a 22mer huMUC1 peptide with two immune dominant regions (PDTR and GSTA). ate with the d GSTA) 1-d sialylated carbohydrate STN on seline-17, Py-MT (polyomavirus middle 'I' antigen) and human MUC1 double transgenic mice expressing human tumor-associated SAUDI on breast tumor tissue served as a preclirlical breast cancer model.