Pérez Sáez Juan M, Hockl Pablo F, Cagnoni Alejando J, Méndez Huergo Santiago P, García Pablo A, Gatto Sabrina G, Cerliani Juan P, Croci Diego O, Rabinovich Gabriel A
Laboratorio de Inmunopatología, Instituto de Biología y Medicina Experimental (IBYME), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), C1428ADN, Buenos Aires, Argentina.
Laboratorio de Glicómica Funcional y Molecular, Instituto de Biología y Medicina Experimental (IBYME), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), C1428ADN, Buenos Aires, Argentina.
Angiogenesis. 2021 Feb;24(1):1-5. doi: 10.1007/s10456-020-09749-3. Epub 2020 Oct 1.
Galectins, a family of highly conserved β-galactoside-binding proteins, control tumor progression by modulating different hallmarks of cancer. Galectin-1 (Gal-1), a proto-type member of this family, plays essential roles in tumor angiogenesis and immunosuppression by cross-linking glycosylated receptors on the surface of endothelial and immune cells. Targeted disruption of Gal-1 suppresses tumor growth by counteracting aberrant angiogenesis and reinforcing antitumor immunity in several experimental settings. Given the multiple therapeutic benefits associated with Gal-1 blockade, several Gal-1 inhibitors, including glycan-based competitors, antagonistic peptides, aptamers and neutralizing monoclonal antibodies, have been designed and evaluated in pre-clinical tumor models. Here we report the biochemical and functional characterization of a newly developed neutralizing anti-human Gal-1 monoclonal antibody (Gal-1-mAb3), which specifically recognizes a unique epitope in Gal-1 protein and exerts both angioregulatory and immunomodulatory activities. Blockade of Gal-1 function using Gal-1-mAb3, might be relevant not only in cancer but also in other pathologic conditions characterized by aberrant angiogenesis and uncontrolled immunosuppression.
半乳糖凝集素是一类高度保守的β-半乳糖苷结合蛋白家族，通过调节癌症的不同特征来控制肿瘤进展。该家族的原型成员半乳糖凝集素-1（Gal-1），通过交联内皮细胞和免疫细胞表面的糖基化受体，在肿瘤血管生成和免疫抑制中发挥重要作用。在多种实验环境中，靶向破坏Gal-1可通过对抗异常血管生成和增强抗肿瘤免疫力来抑制肿瘤生长。鉴于Gal-1阻断具有多种治疗益处，已设计了几种Gal-1抑制剂，包括基于聚糖的竞争者、拮抗肽、适体和中和单克隆抗体，并在临床前肿瘤模型中进行了评估。在此，我们报告了一种新开发的中和抗人Gal-1单克隆抗体（Gal-1-mAb3）的生化和功能特性，该抗体特异性识别Gal-1蛋白中的一个独特表位，并发挥血管调节和免疫调节活性。使用Gal-1-mAb3阻断Gal-1功能，可能不仅与癌症有关，还与其他以异常血管生成和不受控制的免疫抑制为特征的病理状况有关。
