Multifunctional Glycoconjugates for Recruiting Natural Antibodies against Cancer Cells.

We have developed a fully synthetic and multifunctional antibody-recruiting mol. (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, resp. By using a stepwise approach, we have first demonstrated the importance of multivalency for efficient recognition with naturel IgM and αvβ3 integrin expressing M21 tumor cell line. Once covalently conjugated by click chem., 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.

Références

Titre
Multifunctional Glycoconjugates for Recruiting Natural Antibodies against Cancer Cells.
Type de publication
Article de revue
Année de publication
2019
Revue
Chem. - Eur. J.
Volume
25
Pagination
15508–15515
ISSN
0947-6539
Soumis le 15 janvier 2020