A C‐Linked Disaccharide Analogue of Thomsen–Friedenreich Epitope Induces a Strong Immune Response in Mice

Abstract

Anticancer vaccine: Antigen 2 made out of a tripeptide of β‐D‐Galp‐(1→3)‐CH2‐α‐D‐GalNAc‐O‐Ser and conjugated with keyhole limpet hemocyanin (KLH) protein induced an early and strong immune response (IgG antibodies) in mice. Antigen 3 made out of an α‐C‐galactoside analogue did not induce such an immune response (see scheme).

A Cancer Therapeutic Vaccine based on Clustered Tn‐Antigen Mimetics Induces Strong Antibody‐Mediated Protective Immunity

“…One reason for these failures is the sensitivity of TACAs to endogenous glycosidases, which reduces their in vivo bioavailability 22–24. As a consequence, structural modifications to native TACAs, including the use of C‐ and S‐glycosides,25–27 deoxyfluoroglycosides,28–30 truncated antigens,31 or thioether‐bridged mimetics,32 have been proposed to provide structures more stable than those of the parent antigens without interfering with their B‐cell immunogenicity 33. 34…”

Synthesis, conformational analysis and in vivo assays of an anti-cancer vaccine that features an unnatural antigen based on an sp2-iminosugar fragment

“…17 Given that the O-glycosidic bond is particularly sensitive to enzymatic degradation in biological media, the incorporation of GalNAc moieties chemically modied in the anomeric region into carbohydrate-based cancer vaccines has attracted much attention in recent years. [18][19][20][21][22] These modications included the use of C-and Sglycosides [23][24][25] or deoxyuoroglycosides, 26-31 among others. We have recently contributed to this eld by reporting the rst examples of Tn antigens that feature a serine or a threonine glycosylated with a bicyclic sp 2 -iminosugar moiety with a substitution and congurational pattern of structural complementarity to a-GalNAc (a-sp 2 GalNAc), 32 namely compound 1a and the corresponding mucin-related glycopeptide 2a (Fig.…”

A Cancer Therapeutic Vaccine based on Clustered Tn‐Antigen Mimetics Induces Strong Antibody‐Mediated Protective Immunity

“…[21] One reason for these failures is the sensitivity of TACAs to endogenous glycosidases, which reduces their in vivo bioavailability. [22][23][24] As a consequence, structural modifications to native TACAs, including the use of C-and S-glycosides, [25][26][27] deoxyfluoroglycosides, [28][29][30] truncated antigens, [31] or thioether-bridged mimetics, [32] have been proposed to provide structures more stable than those of the parent antigens without interfering with their B-cell immunogenicity. [33,34] In this study, we hypothesized that TACA-based vaccines displaying mimetics instead of native Tn antigens could be more resistant to enzymatic degradation.…”