FUC1 Antibody

Mechanisms of Action

Fucose-targeting antibodies modulate immune responses through:

Cancer Immunotherapy

• BMS-986012: A nonfucosylated anti-FucGM1 antibody shows efficacy in small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). FucGM1 expression correlates with therapeutic response .

• HLA-DRB1 Fucosylation: In melanoma, fucosylation of HLA-DRB1 is required for CD4+ T cell-mediated immunity. Fucosylation inhibitors (e.g., l-fucose) enhance antitumor responses .

Infectious Disease Diagnostics

• Schistosome Oligofucosides: Antibodies binding α-(1-2)-linked tetra-fucosides show high specificity for S. mansoni infections. Longer glycan chains improve binding affinity .

• Core Fucose in IgG: Deficiency in IgG core fucosylation (detected via specific antibodies) is linked to pulmonary diseases and CCL2 regulation .

Autoimmune and Inflammatory Disorders

• Fc-Silenced Antibodies: Mutations in IgG1 (e.g., L234F/L235E) reduce FcγR binding, minimizing off-target inflammation. Examples include XmAb5871 (anti-CD19) for lupus .

Comparative Analysis of Fucose-Targeting Antibodies

Clinical Relevance and Future Directions

• Therapeutic Potential: Nonfucosylated antibodies (e.g., BMS-986012) are being tested in phase III trials for enhanced ADCC efficacy .

• Diagnostic Tools: Antibodies against pathogen-specific glycans (e.g., Schistosoma) could improve disease monitoring .

• Biomarker Discovery: Core fucose levels in IgG may serve as a biomarker for pulmonary diseases .

Challenges and Considerations

• Glycan Complexity: Fucose residues exist in diverse glycan contexts, requiring precise epitope mapping .

• Fc Engineering Trade-offs: Silencing effector functions may reduce therapeutic efficacy in certain contexts .

• Species-Specific Variations: Human vs. murine Fc interactions differ, necessitating preclinical validation .