Synthesis and immunostimulating activity of a thioglycolipopeptide glycomimetic as a potential anticancer vaccine derived from Tn antigen

The Tn epitope is one of the tumor associated O-linked cell surface glycope ptides. It is expressed in over 70% of human epithelial cancers such as lun g, colon, stomach and breast carcinomas. The glycosidic linkage of the Tn a ntigen, between N-acetylgalactosamine and serine or threonine, can be cleav ed either chemically or enzymatically in the presence of glycosidases. The latter case is particularly a problem in vivo. Therefore, it would be of gr eat interest to obtain a metabolically stable analogue of the Tn antigen th at maintains or improves the immunogenic activity of the latter. The purpos e of this work was to synthesize a, totally synthetic vaccine using a chemi cally and metabolically stable glycomimetic of the Tn antigen in which the interglycosidic oxygen was replaced by a sulphur atom (S-Tn). The S-Tn thio glycopeptide was linked to the P3CS immunoadjuvant to obtain the potential S-Tn vaccine. Moreover, we synthesized the natural Tn antigen and derivatiz ed it similarly to obtain the Tn vaccine. Last, we evaluated the immunostim ulating activity of the two synthetic potential vaccines in vitro using cul tured mouse splenocytes. The S-Tn construct showed immunostimulating activi ty comparable, in terms of maximal response, to the Tn analogue. Moreover, due to its higher stability the S-Tn construct reached its maximal effect a t lower doses compared to the Tn analogue.