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Development and Use of a Galectin-1-Specific Nanobody for Tumor Imaging and Elucidating the Role of Galectin-1 in Cancer

Granger Joly de Boissel, Philippine; Nehmé, Rita; Fortier, Marlène; Létourneau, Myriam; Guérin, Brigitte; Dumulon-Perreault, Véronique; Ait-Mohand, Samia; Sarrhini, Otman; Fuselier, Camille; Dumoulin, Alyssa; 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 (2025). Development and Use of a Galectin-1-Specific Nanobody for Tumor Imaging and Elucidating the Role of Galectin-1 in Cancer ACS Pharmacology and Translational Science , vol. ahead . pp. 1-11. DOI: 10.1021/acsptsci.5c00178. (Sous Presse)

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Résumé


Galectin-1 (GAL-1) plays a crucial role in cancer biology, especially in triple-negative breast cancer (TNBC), where it facilitates immune evasion and tumor progression. This study presents G1N1, a novel nanobody that specifically targets GAL-1 and exhibits remarkable affinity and selectivity. G1N1 effectively inhibits GAL-1-induced apoptosis in T cells while leaving GAL-7-induced apoptosis unaffected. Preclinical positron emission tomography (PET) imaging studies indicate that the radiolabeled [64Cu]Cu-NOTA-G1N1 accumulates significantly in breast cancer tumors, highlighting its potential for diagnostic imaging and therapeutic monitoring. Transcriptomic analyses suggest that G1N1 may counteract GAL-1-induced immunosuppression and downregulate chemoresistance-associated genes, particularly those involved in the NF-κB/TNFα signaling pathway, while also decreasing the expression of prometastatic genes like MMP-3. In conclusion, G1N1’s dual functionality as a diagnostic and therapeutic agent emphasizes its promise in personalized medicine, potentially enhancing clinical management strategies for TNBC and other aggressive cancers.

Type de document: Article
Informations complémentaires: This work was supported by the Canadian Institutes of Health Research (CIHR), the Quantum Leap II program of the Consortium Québécois 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: Galectins; nanobodies; cancer; PET imaging; transcriptomics
Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 28 août 2025 19:02
Dernière modification: 28 août 2025 19:02
URI: https://espace.inrs.ca/id/eprint/16582

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