Anti-tumor immunity provided by a synthetic multiple antigenic glycopeptide displaying a tri-Tn glycotope

In many cancer cells the alteration of glycosylation processes leads to the expression of cryptic carbohydrate moieties, which make them good targets for immune intervention. Identification of cancer-associated glycotopes as well as progress in chemical synthesis have opened up the way for the devel opment of fully synthetic immunogens that can induce anti-saccharide immune responses. Here, we synthesized a dendrimeric multiple antigenic glycopept ide (MAG) containing the Tn Ag O-linked to a CD4(+) T cell epitope, This MA G is based on three consecutive Tn moieties (tri-Tn) corresponding to the g lycotope recognized by an mAb (MLS 128) produced against the LS180 colon ca rcinoma cell line, The Abs induced by this MAG recognized murine and human tumor cell lines expressing the Tn Ag, Prophylactic vaccination using MAG p rovided protection of mice against tumor challenge, When used in active spe cific immunotherapy, the MAG carrying the tri-Tn glycotope was much more ef ficient than the mono-Tn analogue in promoting the survival of tumor-bearin g mice. Furthermore, in active specific immunotherapy, a linear glycopeptid e carrying two copies of the tri-Tn glycotope was shown to be poorly effici ent compared with the dendrimeric MAG, Therefore, both the clustering of ca rbohydrate Ags and the way they are displayed seem to be important paramete rs for stimulating efficient anti-saccharide immune responses.