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

2801 West Bancroft Street, Department of Chemistry and Biochemistry and School of Green Chemistry and Engineering, The University of Toledo, Toledo, OH 43606, USA
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These authors contributed equally to this work.
Molecules 2020, 25(6), 1319; https://doi.org/10.3390/molecules25061319
Received: 20 February 2020 / Revised: 11 March 2020 / Accepted: 12 March 2020 / Published: 13 March 2020
(This article belongs to the Special Issue Targeting Carbohydrate–Protein Interactions)
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. View Full-Text
Keywords: cancer vaccine; tumor associated carbohydrate antigen; zwitterionic polysaccharide; C-type lectin receptor; multivalent vaccine cancer vaccine; tumor associated carbohydrate antigen; zwitterionic polysaccharide; C-type lectin receptor; multivalent vaccine
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MDPI and ACS Style

Kleski, K.A.; Trabbic, K.R.; Shi, M.; Bourgault, J.-P.; Andreana, P.R. Enhanced Immune Response Against the Thomsen-Friedenreich Tumor Antigen Using a Bivalent Entirely Carbohydrate Conjugate. Molecules 2020, 25, 1319.

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