Enhanced Immune Response Against the Thomsen-Friedenreich Tumor Antigen Using a Bivalent Entirely Carbohydrate Conjugate.

Autor: Kleski KA; 2801 West Bancroft Street, Department of Chemistry and Biochemistry and School of Green Chemistry and Engineering, The University of Toledo, Toledo, OH 43606, USA., Trabbic KR; 2801 West Bancroft Street, Department of Chemistry and Biochemistry and School of Green Chemistry and Engineering, The University of Toledo, Toledo, OH 43606, USA., Shi M; 2801 West Bancroft Street, Department of Chemistry and Biochemistry and School of Green Chemistry and Engineering, The University of Toledo, Toledo, OH 43606, USA., Bourgault JP; 2801 West Bancroft Street, Department of Chemistry and Biochemistry and School of Green Chemistry and Engineering, The University of Toledo, Toledo, OH 43606, USA., Andreana PR; 2801 West Bancroft Street, Department of Chemistry and Biochemistry and School of Green Chemistry and Engineering, The University of Toledo, Toledo, OH 43606, USA.
Jazyk: angličtina
Zdroj: Molecules (Basel, Switzerland) [Molecules] 2020 Mar 13; Vol. 25 (6). Date of Electronic Publication: 2020 Mar 13.
DOI: 10.3390/molecules25061319
Abstrakt: The Thomsen-Friedenreich (TF) antigen is a key target for the development of anticancer vaccines, and this ongoing challenge remains relevant due to the poor immunogenicity of the TF antigen. To overcome this challenge, we adopted a bivalent conjugate design which introduced both the TF antigen and the Thomsen-nouveau (Tn) antigen onto the immunologically relevant polysaccharide A1 (PS A1). The immunological results in C57BL/6 mice revealed that the bivalent, Tn-TF-PS A1 conjugate increased the immune response towards the TF antigen as compared to the monovalent TF-PS A1. This phenomenon was first observed with enzyme-linked immunosorbent assay (ELISA) where the bivalent conjugate generated high titers of IgG antibodies where the monovalent conjugate generated an exclusive IgM response. Fluorescence-activated cell sorting (FACS) analysis also revealed increased binding events to the tumor cell lines MCF-7 and OVCAR-5, which are consistent with the enhanced tumor cell lysis observed in a complement dependent cytotoxicity (CDC) assay. The cytokine profile generated by the bivalent construct revealed increased pro-inflammatory cytokines IL-17 and IFN-γ. This increase in cytokine concentration was matched with an increase in cytokine producing cells as observed by ELISpot. We hypothesized the mechanisms for this phenomenon to involve the macrophage galactose N -acetylgalactosamine specific lectin 2 (MGL2). This hypothesis was supported by using biotinylated probes and recombinant MGL2 to measure carbohydrate-protein interactions.
Databáze: MEDLINE
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