Synthesis and immunological evaluation of an antitumor neoglycopeptide vaccine bearing a novel homoserine Tn antigen.

Sophie Vichier-Guerre (1) , Richard Lo-Man (2) , Valérie Huteau (1) , Edith Dériaud (2) , Claude Leclerc (2) , Sylvie Bay (1)

1 Chimie Organique
2 Biologie des Régulations Immunitaires

As part of our program on Tn-specific anti-tumor immunotherapy, our aim was to vary the nature of the aglyconic part of the tumor-associated Tn antigen (alpha-d-GalNAc-Ser/Thr). This report describes the synthesis of Fmoc-hSer-(alpha-d-GalNAc)-OH (4) in 19% overall yield from protected aspartic acid. The building block 4 was incorporated as trimeric clusters into a glycopeptide vaccine [MAG:Tn(hSer)3-PV], using solid-phase peptide synthesis. When injected in mice, the resulting MAG induces a strong antibody response, which recognizes native tumor-associated antigens (TAA) at the surface of human tumor cells. This approach may be extended to the use of other nonnatural TAA in order to improve half-life of synthetic anti-cancer vaccines.

Sophie Vichier-Guerre, Richard Lo-Man, Valérie Huteau, Edith Dériaud, Claude Leclerc, et al.. Synthesis and immunological evaluation of an antitumor neoglycopeptide vaccine bearing a novel homoserine Tn antigen.. Bioorganic and Medicinal Chemistry Letters, 2004, 14 (13), pp.3567-70. ⟨10.1016/j.bmcl.2004.04.047⟩. ⟨pasteur-00166850⟩