Development of Galectin-7-Specific Nanobodies: Implications for Immunotherapy and Molecular Imaging in Cancer

Nehmé, Rita; Fortier, Marlène; Létourneau, Myriam; Fuselier, Camille; Granger Joly de Boissel, Philippine; Dumoulin, Alyssa; Guérin, Brigitte; Dumulon-Perreault, Véronique; Ait-Mohand, Samia; Sarrhini, Otman; Larda, Sacha T; Castellanos Villamizar, Yarileny; Bernier, Michel; Porębska, Natalia; Opaliński, Łukasz; Chatenet, David ORCID: https://orcid.org/0000-0002-7270-4328; Doucet, Nicolas ORCID: https://orcid.org/0000-0002-1952-9380 et St-Pierre, Yves ORCID: https://orcid.org/0000-0002-1948-2041 (2025). Development of Galectin-7-Specific Nanobodies: Implications for Immunotherapy and Molecular Imaging in Cancer Journal of Medicinal Chemistry , vol. 68 , nº 8. pp. 8484-8496. DOI: 10.1021/acs.jmedchem.5c00071.

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Résumé

Galectins play significant roles in regulating immune responses, posing challenges for cancer immunotherapy. The development of galectin inhibitors has been limited by their high structural homology and the lack of noninvasive imaging tools to identify potential responsive patients. We developed 12 galectin-7-specific inhibitors using nanobodies (Nbs) and identified G7N8 as the lead Nb. G7N8 was conjugated with the NOTA chelator, labeled with copper-64 ([(64)Cu]Cu), and used as a radiotracer for PET imaging in a triple-negative breast cancer (TNBC) mouse model. Nbs demonstrated high affinity for galectin-7, with no binding activity for other galectins tested. The lead Nbs inhibited galectin-7 binding to T-cell glycoreceptors and reduced subsequent apoptosis. PET imaging with [(64)Cu]Cu-NOTA-G7N8 showed selective radiotracer accumulation at 20 h (P = 0.001). We developed galectin-7-specific Nbs that inhibit T-cell apoptosis and enable PET imaging of TNBC, providing novel tools for investigating immune regulation and enhancing cancer immunotherapy.

Type de document:	Article
Informations complémentaires:	Funding This work was supported by the Canadian Institutes of Health Research (CIHR), the Quantum Leap II program of the Consortium Québé cois sur la Découverte du Médicament (CQDM), GlycoNet, and the Natural Sciences and Engineering Research Council of Canada (NSERC) (Discovery grant RGPIN-2022-04368, to N.D.). Part of this work was also supported by the Molecular Interactions and Materials Characterization Facility (MIMC) of INRS, which is funded by a Canada Foundation for Innovation (CFI) Major Science Initiatives (MSI) fund awarded to GlycoNet Integrated Services. N.D. acknowledges support from a Research Scholar Senior Career Award (number 281993) of the Fonds de Recherche Québec-Santé (FRQS).
Mots-clés libres:	Antigens; Apoptosis; Biological imaging; Cancer; Rodent models
Centre:	Centre INRS-Institut Armand Frappier
Date de dépôt:	07 juill. 2025 18:51
Dernière modification:	07 juill. 2025 18:51
URI:	https://espace.inrs.ca/id/eprint/16451

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