GASA9 Antibody

Introduction to Galectin-9 (Gal-9) Antibodies

Galectin-9 (Gal-9) is a β-galactoside-binding lectin that modulates immune responses by interacting with receptors such as TIM-3 and dectin-1. Anti-Gal-9 antibodies are engineered to neutralize Gal-9, thereby counteracting immunosuppression in cancer and chronic inflammation. These antibodies represent a novel class of immune checkpoint inhibitors with distinct mechanisms compared to PD-1/PD-L1 or CTLA-4 blockers .

Antibody Structure

Anti-Gal-9 antibodies follow the canonical Y-shaped immunoglobulin structure:

• Fab region: Contains variable domains (VH and VL) that bind Gal-9’s N-terminal carbohydrate-recognition domain (N-CRD) .

• Fc region: Mediates interactions with Fc receptors and complement proteins, enhancing immune effector functions .

Key Mechanistic Insights

In Vitro Efficacy

• T-cell Protection: Antibodies (e.g., clones 292-13, 292-18A) inhibit Gal-9-induced apoptosis in CD4+ and CD8+ T cells at concentrations as low as 1 μg/mL .

• Tumor Cell Killing: In coculture assays, Gal-9 antibodies promote T-cell-mediated cytotoxicity against cancer cells .

Preclinical Models

Antibody Clones and Performance

Limitations

• Target Cross-Reactivity: Some antibodies (e.g., mAb114) bind sGP, a decoy protein released by viruses like Ebola, potentially reducing efficacy .

• Glycosylation Impact: Fc-region glycosylation (e.g., IgG N-glycosylation) affects antibody stability and effector functions .

Emerging Opportunities

• Bispecific Antibodies: CrossMab technology could enable dual targeting of Gal-9 and other checkpoints (e.g., PD-1) .

• Combination Therapies: Synergy with costimulatory agonists (e.g., GITR) may enhance antitumor responses .