A fully synthetic immunogen carrying a carcinoma-associated carbohydrate for active specific immunotherapy

Aberrant glycosylation of mucins leads to the exposure of cryptic carbohydr ate antigens at the surface of carcinoma cells, which, therefore, represent patent targets for anticancer therapeutic vaccines. To date, the developme nt of immunogens to stimulate immune response to such saccharidic antigens is based on carbohydrate conjugation to carrier proteins, However, these tr aditional protein conjugates are poorly defined in chemical composition and structure, As an alternative, we synthesized a multiple antigenic O-linked glycopeptide (MAG) carrying the carbohydrate Tn antigen associated with a CD4(+) T-cell epitope (MAG:Tn-PV). This fully synthetic immunogen is highly defined in composition and carries a high saccharidic epitope ratio over t he entire molecule. The MAG:Tn-PV was able to induce anti-Tn Ige antibodies that recognize human tumor cell lines. A therapeutic immunization protocol performed with this fully synthetic immunogen increased the survival of tu mor-bearing mice. Thus, the accurately defined and versatile MAG system rep resents an efficient strategy to induce carbohydrate-specific antitumor imm une responses but may also be applicable to the prevention of infectious di seases, if it is based on bacterial oligosaccharides.