Synthesis and immunological evaluation of an antitumor neoglycopeptide vaccine bearing a novel homoserine Tn antigen.
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.
Vichier-Guerre
Sophie
S
Unité de Chimie Organique URA CNRS 2128, Institut Pasteur, 28, rue du Dr Roux, 75724 Paris 15, France.
Lo-Man
Richard
R
Huteau
Valérie
V
Dériaud
Edith
E
Leclerc
Claude
C
Bay
Sylvie
S
D000818:Animals; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000737:chemistry / Q000276:immunology*; D019496:Cancer Vaccines / Q000737:chemistry* / Q000276:immunology / Q000494:pharmacology; D045744:Cell Line, Tumor; D006020:Glycopeptides / Q000138:chemical synthesis* / Q000276:immunology / Q000494:pharmacology; D006207:Half-Life; D006714:Homoserine / Q000737:chemistry*; D006801:Humans; D016233:Immunotherapy, Active
D015295:Antigens, Tumor-Associated, Carbohydrate; D019496:Cancer Vaccines; D006020:Glycopeptides; C040286:Tn antigen; D006714:Homoserine