Syracuse

Multifunctional Glycoconjugates for Recruiting Natural Antibodies against Cancer Cells

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Liet, Benjamin | Laigre, Eugénie | Goyard, David | Todaro, Biagio | Tiertant, Claire | Boturyn, Didier | Berthet, Nathalie | Renaudet, Olivier

Edité par CCSD ; Wiley-VCH Verlag -

International audience. We have developed af ully synthetic and multifunctional antibody-recruiting molecule (ARM) to guide natural antibodies already present in the blood stream against cancer cells withoutp re-immunization. Our ARM is composed of antibody andt umor bindingm odules (i.e.,A BM and TBM) displaying clustered rhamnose and cyclo-RGD, respectively.B yu sing as tepwise approach, we have first demonstrated the importance of multivalency for efficient recognition with naturel IgM and a v b 3 integrin expressing M21 tumor cell line. Once covalently conjugatedb yc lick chemistry ,w ec onfirmed by flow cytometry and confocal microscopy that the recognitionp roperties of both the ABM and TBM are conserved, and more importantly,t hat the resulting ARM promotes the formation of at ernary complex between naturalI gM and cancerc ells, which is required for the stimulation of the cytotoxic immune response in vivo. Due to the efficiency of the syntheticp rocess, al arger diversity of heterovalentl igands could be easily explored by using the same multivalent approacha nd could open new perspectives in this field.

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