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Development of Galectin-7-Specific Nanobodies: Implications for Immunotherapy and Molecular Imaging in Cancer
Rita Nehmé1, Marlène Fortier1, Myriam Létourneau1
1INRS─Centre Armand-Frappier Santé Biotechnologie, Laval, Québec H7 V 1B7, Canada.
Abstract:
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 ([64Cu]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 [64Cu]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.
Insights
Researchers developed novel galectin-7 specific nanobodies (Nbs) that inhibit T-cell apoptosis and enable PET imaging for triple-negative breast cancer (TNBC). These tools aid in cancer immunotherapy by identifying responsive patients.
Area of Science:
- Immunology
- Oncology
- Radiochemistry
Background:
- Galectins are key regulators of immune responses and present challenges in cancer immunotherapy.
- Developing galectin inhibitors is difficult due to structural similarities and a lack of imaging tools to identify responsive patients.
Purpose of the Study:
- To develop galectin-7 specific inhibitors using nanobodies (Nbs).
- To create a PET imaging tracer for identifying patients responsive to galectin-targeted therapies.
- To investigate the role of galectin-7 in triple-negative breast cancer (TNBC) immune evasion.
Main Methods:
- Developed 12 galectin-7 specific nanobodies (Nbs), identifying G7N8 as the lead.
- Conjugated G7N8 with NOTA chelator and labeled with copper-64 ([64Cu]Cu) for PET imaging.
- Evaluated Nb affinity, specificity, and inhibitory function in vitro and in a TNBC mouse model.
Main Results:
- Nbs showed high affinity and specificity for galectin-7, inhibiting T-cell glycoreceptor binding and reducing apoptosis.
- [64Cu]Cu-NOTA-G7N8 PET imaging demonstrated selective radiotracer accumulation in TNBC models.
- The developed Nbs effectively target galectin-7 and can be used for non-invasive imaging.
Conclusions:
- Galectin-7 specific nanobodies offer a dual approach for inhibiting T-cell apoptosis and enabling PET imaging in TNBC.
- These novel tools can advance the understanding of immune regulation in cancer.
- The findings provide new avenues for enhancing cancer immunotherapy by identifying patient populations likely to respond to treatment.
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