GALS3 Antibody: Definition and Types
GALS3 antibodies are immunoglobulins designed to bind and inhibit Galectin-3. Key types include:
Antibody Type Examples Target Applications References Monoclonal (mAb) D11, E07, 14D11, MAB11541 Carbohydrate-binding domain Neutralizing Galectin-3 in SSc, cancer Polyclonal (pAb) AF1154, ab209344 Multiple epitopes ELISA, Western blot, IHC
Key Features :
MAB11541 : Detects human Gal-3 in ELISA and Western blot (28–38 kDa band) with no cross-reactivity to other galectins .
14D11 : High-affinity mAb blocking Gal-3-MUC16 interaction, reducing cancer cell invasion .
ab209344 : Rabbit recombinant mAb validated via knockout (KO) cell lines, suitable for IP and ICC .
Therapeutic Applications
GALS3 antibodies show efficacy in preclinical models of fibrosis, cancer, and autoimmune diseases.
2.1. Systemic Sclerosis (SSc)
In a hypochlorous acid (HOCl)-induced SSc mouse model, D11 and E07 mAbs reduced:
Skin thickening by 40% and lung collagen deposition by 30% .
Cytokine levels : IL-5 (↓45%) and IL-6 (↓35%) .
Pulmonary macrophages and neutrophil-to-lymphocyte ratio (NLR) .
2.2. Cancer
14D11 mAb demonstrated:
Inhibited invasion : Matrigel invasion ↓ in SKOV3 (ovarian) and MDA-MB-231 (breast) cells .
Blocked signaling : Reduced AKT/ERK1/2 phosphorylation .
Metastasis suppression : Prolonged survival in murine models of lung metastasis .
2.3. IgG4-Related Disease (IgG4-RD)
Anti-Gal-3 IgG4 autoantibodies correlate with:
Mechanisms of Action
GALS3 antibodies disrupt Gal-3’s proinflammatory and profibrotic roles:
Pathway Antibody Effect Evidence Neutrophil recruitment ↓ Migration via DAMP blockade Reduced neutrophil influx in sepsis Fibroblast activation ↓ Collagen synthesis ↓ Skin/lung fibrosis in SSc models Cancer cell adhesion Disrupted Gal-3-MUC16 interaction ↓ Invasion in breast/ovarian cancer Macrophage activation ↓ Pro-inflammatory cytokines ↓ IL-5/IL-6 in SSc
4.1. Biomarker Utility
Gal-3 serum levels correlate with:
SSc severity : High levels linked to pulmonary/cardiac dysfunction .
Prognosis : Independent predictor of mortality in SSc .
Cancer : Elevated in MUC16+ tumors (e.g., ovarian, breast) .
4.2. Limitations
Cross-reactivity : Early pAbs (e.g., AF1154) may bind non-specific epitopes .
Tissue penetration : Systemic delivery challenges in fibrotic organs .
Isotype dependency : IgG4 subclass dominance in IgG4-RD complicates targeting .
Future Directions
Humanized mAbs : Transitioning murine antibodies (e.g., 14D11) to human-compatible formats.
Combination therapies : Pairing Gal-3 inhibitors with antifibrotics (e.g., pirfenidone) .
Personalized medicine : Stratifying SSc/IgG4-RD patients based on Gal-3 interactome signatures .