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

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