l-Rhamnose Enhances the Immunogenicity of Melanoma-Associated Antigen A3 for Stimulating Antitumor Immune Responses

Abstract

Vaccines based on melanoma-associated antigens (MAGEs) present a promising strategy for tumor immunotherapy, albeit with weak immunogenicity. In this study, the xenoantigen L-rhamnose (Rha) was chemically conjugated with truncated MAGE-A3 (tMAGE-A3) to generate Rha-tMAGE-A3. The product showed good antigenicity with anti-Rha antibodies purified from human serum. FITC-labeled Rha-tMAGE-A3 was detected in THP-1 human macrophage cells via the anti-Rha antibody-dependent antigen uptake process. Furthermore, peripheral blood mononuclear cells (PBMCs) stimulated with Rha-tMAGE-A3 in the presence of anti-Rha antibodies showed better cytotoxicity toward A375 human melanoma cells surfaced by MAGE-A3 antigen compared to PBMCs stimulated with tMAGE-A3. All data reveal that linking of Rha epitopes to MAGE enhances the immunogenicity of MAGE by harnessing the immune effector functions of human naturally existing anti-Rha antibodies. Rha epitopes could become immunogenicity enhancers of tumor associated antigens in the development of tumor immunotherapies.

Exopolysaccharide, Isolated From a Novel Strain Bifidobacterium breve lw01 Possess an Anticancer Effect on Head and Neck Cancer – Genetic and Biochemical Evidences

“…The patients with low level of d-mannose have higher risk of recurrence and death (Gu et al, 2017). Besides, rhamnose has also been reported to have anti-tumor activity, since it can enhance the immunogenicity of melanoma-associated antigen A3, which stimulates antitumor immune responses (Zhang et al, 2016). The galactose is widely used backbone of the nanocarrier in cancer therapy, beneficial for targeted therapy of tumors (Jain et al, 2018).…”

Fucosylated ubiquitin and orthogonally glycosylated mutant A28C: conceptually new ligands for Burkholderia ambifaria lectin (BambL)

“…Synthesis of rhamnosyl derivative 13. Since rhamnose-containing polysaccharides showed significant modulatory activities in macrophages in in vitro inflammatory models, 20,21 we also introduced this monosaccharide onto Ub to build up a conceptually new BambL inhibitor with immunomodulating properties. We thus biotechnologically expressed the Ub mutant A28C, where alanine 28 was replaced by one cysteine residue (see SI).…”

“…In fact, rhamnose-containing plant polysaccharides have recently been demonstrated to modulate activities in macrophages in in vitro inflammatory models. 20,21 The three ligands, namely Fuc-Ub, Rha-A28C and Fuc-Rha-A28C, in vitro biologically characterized, have been tested for their ability to modulate macrophage activation either in resting conditions or after lipopolysaccharide (LPS) stimuli.…”

Synthesis of C‐Glycosyl Amino Acid Building Blocks Suitable for the Solid‐Phase Synthesis of Multivalent Glycopeptide Mimics

“…[4,10,11] Another example is the exploitation of the abundance of the circulating anti-L-rhamnose antibodies in human blood, [12,13] that can be recruited using multivalent rhamnose conjugates. [14][15][16][17][18] We reasoned that the development of automated solid phase techniques to generate clusters of (different) carbohydrates would be attractive to rapidly assemble multivalent glycoconjugates. [6] Ponader et al developed a solid-phase synthesis method to obtain homo-and hetero-multivalent glycooligomers using alkyne-functionalized building blocks functionalized by a Cu-catalyzed azide-alkyne [2+3] cycloaddition with mannose, galactose or glucose synthons equipped with an azide.…”