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

半乳糖凝集素-1（Galectin-1，简称GAL-1）在癌症生物学领域发挥关键作用，尤其在三阴性乳腺癌（triple-negative breast cancer，TNBC）中，可介导免疫逃逸与肿瘤进展。本研究报道了一种靶向GAL-1的新型纳米抗体（nanobody）G1N1，其展现出优异的亲和力与选择性。G1N1可有效抑制GAL-1诱导的T细胞凋亡，却不会影响GAL-7诱导的细胞凋亡过程。临床前正电子发射断层扫描（positron emission tomography，PET）成像研究显示，放射性标记的[64Cu]Cu-NOTA-G1N1可在乳腺癌肿瘤组织中显著富集，凸显其在诊断成像与治疗监测领域的应用潜力。转录组分析结果表明，G1N1可拮抗GAL-1诱导的免疫抑制，并下调化疗耐药相关基因的表达，尤其是参与NF-κB/TNFα信号通路的相关基因；同时还可降低基质金属蛋白酶-3（MMP-3）等促转移基因的表达水平。综上，G1N1兼具诊断与治疗双重功能，彰显其在个性化医疗中的应用前景，有望优化三阴性乳腺癌及其他侵袭性癌症的临床管理策略。