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Multifunctional Glycoconjugates for Recruiting Natural Antibodies against Cancer Cells
Author(s) -
Liet Benjamin,
Laigre Eugénie,
Goyard David,
Todaro Biagio,
Tiertant Claire,
Boturyn Didier,
Berthet Nathalie,
Renaudet Olivier
Publication year - 2019
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201903327
Subject(s) - glycoconjugate , antibody , cancer cell , flow cytometry , chemistry , immune system , cytotoxic t cell , rhamnose , cancer , biology , microbiology and biotechnology , cancer research , biochemistry , immunology , in vitro , galactose , genetics
We have developed a fully synthetic and multifunctional antibody‐recruiting molecule (ARM) to guide natural antibodies already present in the blood stream against cancer cells without pre‐immunization. Our ARM is composed of antibody and tumor binding modules (i.e., ABM and TBM) displaying clustered rhamnose and cyclo‐RGD, respectively. By using a stepwise approach, we have first demonstrated the importance of multivalency for efficient recognition with naturel IgM and α v β 3 integrin expressing M21 tumor cell line. Once covalently conjugated by click chemistry, we confirmed by flow cytometry and confocal microscopy that the recognition properties of both the ABM and TBM are conserved, and more importantly, that the resulting ARM promotes the formation of a ternary complex between natural IgM and cancer cells, which is required for the stimulation of the cytotoxic immune response in vivo. Due to the efficiency of the synthetic process, a larger diversity of heterovalent ligands could be easily explored by using the same multivalent approach and could open new perspectives in this field.