GLR2.9 Antibody

Galectin-9 as a Therapeutic Target

Galectin-9 is a tandem-repeat galectin family member that interacts with receptors like Tim-3 and CD44, modulating immune responses and promoting tumor immune escape . Its overexpression in cancers (e.g., AML, solid tumors) correlates with immunosuppression and resistance to checkpoint inhibitors .

Key Mechanisms of Gal-9 in Cancer

• Induces apoptosis of Th1 cells and enhances regulatory T-cell (Treg) expansion .

• Promotes myeloid-derived suppressor cell (MDSC) differentiation and M2 macrophage polarization .

• Sustains leukemic stem cell self-renewal in AML .

Anti-Galectin-9 Antibodies in Development

Several antibodies targeting Gal-9 are under investigation for their therapeutic potential:

HFB9-2 (HiFiBiO Therapeutics)

• Structure: Humanized monoclonal antibody with sub-nanomolar affinity for Gal-9 .

• Mechanism: Blocks Gal-9 binding to Tim-3 and CD44, inhibiting Th1 apoptosis and Treg expansion .

• Efficacy: Demonstrated anti-tumor activity in syngeneic mouse models (e.g., WEHI-164) and synergy with anti-PD-1 therapy .

ab227046 (Abcam) and MAB20454 (R&D Systems)

• Applications: Validated for Western blot, IHC, flow cytometry, and immunofluorescence .

• Specificity: Detects Gal-9 isoforms (~36–45 kDa) and degraded fragments (13–15 kDa) .

Clinical and Translational Insights

• AML Patients: Elevated serum Gal-9 levels correlate with disease progression and drop during remission .

• Biomarker Potential: Gal-9 expression in tumor-infiltrating immune cells (e.g., macrophages, T cells) predicts immunosuppressive microenvironments .

Challenges and Future Directions

• Resistance Mechanisms: Gal-9/Tim-3 axis contributes to primary and acquired resistance to PD-1/PD-L1 inhibitors .

• Therapeutic Strategies: Combining Gal-9-neutralizing antibodies (e.g., HFB9-2) with existing immunotherapies may enhance efficacy .