Gal-1 antibodies are monoclonal or polyclonal immunoglobulins that bind to Gal-1, a 14 kDa protein encoded by the LGALS1 gene. Gal-1 facilitates tumor immune evasion, angiogenesis, and metastasis by interacting with glycosylated receptors on endothelial cells (ECs) and immune cells . Antibodies against Gal-1 block these interactions, offering potential therapeutic benefits in cancer and inflammatory diseases.
Key advancements in Gal-1 antibody development include:
Gal-1-mAb3: A neutralizing monoclonal antibody that binds a unique Gal-1 epitope, disrupting its angiogenic and immunosuppressive functions. It inhibits Gal-1 binding to VEGFR2 and neuropilin-1 (NRP-1), critical for VEGF-like signaling in ECs .
αhGal-1: A porcine/human cross-reactive antibody targeting a conserved epitope (peptide sequence: SKDGGAWG). It shows no cross-reactivity with other galectins (Gal-2, -3, -4, -7) .
| Antibody | Epitope Specificity | Cross-Reactivity | Application |
|---|---|---|---|
| Gal-1-mAb3 | Unique conformational epitope | None | Neutralization in cancer models |
| αhGal-1 | SKDGGAWG peptide | Porcine, human | Immunohistochemistry, Western blot |
Gal-1 antibodies exert dual effects:
Angiogenesis Inhibition: Block Gal-1 binding to EC receptors (e.g., VEGFR2), reducing tumor vascularization .
Immune Modulation: Reverse Gal-1-mediated immunosuppression by enhancing T cell infiltration and reducing regulatory T (Treg) cell activity .
STAT Signaling: Gal-1 knockdown reduces STAT1 activation in tumor ECs, downregulating PD-L1 and other immune checkpoint ligands .
Warburg Effect: In glioblastoma stem cells (GSCs), Gal-1 antibodies disrupt hypoxia-induced metabolic reprogramming by reducing CA-IX expression .
Tumor Growth Reduction: In syngeneic lung adenocarcinoma models, Gal-1 inhibition via antibodies reduced tumor volume by 40–60% and enhanced NK cell activity .
Synergy with Immunotherapy: Anti-Gal-1 combined with anti-PD1 improved T cell infiltration and response rates in head and neck cancer models .
Rheumatoid Arthritis (RA): Serum Gal-1 levels are elevated in RA patients (19.12 ng/ml cutoff for diagnosis; 71% sensitivity, 79% specificity) . Antibodies against Gal-1 may mitigate inflammation by restoring Th1/Th2 balance .
Cancer Prognosis: High Gal-1 expression correlates with poor survival in melanoma, glioblastoma, and lung cancer .
Immune Checkpoint Response: Low Gal-1 levels predict better response to immune checkpoint blockade (ICB) therapy .
Dimerization Stability: Recombinant Gal-1 (rGal-1) requires dimerization for functionality. Engineered forms (e.g., leucine-zippered Gal-1) show improved stability .
Clinical Translation: Only one antibody (Gal-1-mAb3) has entered preclinical trials. Larger human studies are needed to validate diagnostic and therapeutic efficacy .