Dépôt numérique

Development and characterization of galectin-13-specific nanobodies

Fuselier, Camille; Dumoulin, Alyssa; Parent, Alex; Nehmé, Rita; Ajarrag, Samy; Granger Joly de Boissel, Philippine; Chatenet, David ORCID logoORCID: https://orcid.org/0000-0002-7270-4328; Doucet, Nicolas ORCID logoORCID: https://orcid.org/0000-0002-1952-9380 et St-Pierre, Yves ORCID logoORCID: https://orcid.org/0000-0002-1948-2041 (2023). Development and characterization of galectin-13-specific nanobodies In: Annual Meeting of the Society for Glycobiology (SFG), November 05-08, 2023, Hawaii.

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Galectins (GALs) represent a family of evolutionarily conserved lectins that preferentially bind to glycoconjugate residues via their carbohydrate recognition domains (CRDs). Although GALs are known to play many roles during several physiological processes, their overexpression plays an essential role in the progression of several diseases, particularly cancer. Among galectins, galectin-13 (GAL-13) belongs to the subgroup of placental galectins. Their role in placental development and their use as a biomarker for gestational disorders has sparked the interest of many researchers in prenatal research. Initially identified in the syncytiotrophoblast of the placenta, there is increasing evidence that they also play a role in cancer progression. Indeed, cancer and trophoblast cells share several common features like invasive and angiogenic properties, while employing similar strategies to evade immune surveillance. Although it is logical to hypothesize that placental galectins play a role in cancer, the absence of specific inhibitors against GAL-13 has not yet enabled us to study their role in cancer and other diseases. Using sugar compounds as CRD inhibitors seems challenging since placental galectins such as GAL-13 and GAL-16 present the highest sequence homology among galectin family members. An alternative to this problem is to exploit the potential camelid antibodies (also called Nanobodies, Nbs) which have many advantages compared to conventional monoclonal antibodies. Indeed, their unique properties, such as their small size, high stability and high antigen-binding affinity, could allow Nbs to accelerate research on GAL-13 and serve as therapeutic agents. The objectives of our project were to develop Nbs against GAL-13 and an in vitro model to study its role in cancer by identifying Nbs with therapeutic potential. GAL-13-specific Nbs were generated by screening a synthetic camelid library with biotinylated full-length recombinant GAL-13 to find positive VHH clones. A hit-to-lead phase, comprising various biochemical and functional assays, was then used to identify lead Nbs. Our results showed that most, but not all, Nbs inhibited at different levels, the binding of GAL-13 to asialofetuin. A more effective inhibition was observed with selective combinations of Nbs, suggesting that several Nbs target distinct epitopes. We also determined the ability of the Nbs to target linear versus conformational epitopes and their sensitivity to mutations within GAL-13’s glycan binding sites. The binding of the Nbs was specific for GAL-13, although, not surprisingly, some of them also bound GAL-16. In conclusion, we have generated GAL-13-specific Nbs with exciting properties, defining them as specific anti-GAL-13 inhibitors. As such, these Nbs are the first tools that could accelerate fundamental research on GAL-13 and the development of future clinical applications (imaging or therapy) for treating diseases where GAL-13 is overexpressed, notably in cancer.

Type de document: Document issu d'une conférence ou d'un atelier
Informations complémentaires: Affiche scientifique P184 Glycobiology (2023) 33(11):1041
Mots-clés libres: -
Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 08 avr. 2024 15:03
Dernière modification: 08 avr. 2024 15:03
URI: https://espace.inrs.ca/id/eprint/15589

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