Stabilizing the CHI3L1-Gal3BP complex remodels the glioblastoma immune microenvironment and synergizes with PD-1 blockade

Oral LZ6 stabilizes the CHI3L1-Gal3BP complex in orthotopic GL261 glioblastoma, shifting 20 of 24 immune endpoints and extending median survival to 52.4 days.

• Why it matters: CHI3L1 is linked to mesenchymal, treatment-resistant GBM and shapes macrophage programs via galectin-3 or Gal3BP, but the CHI3L1-Gal3BP interaction has not been targeted.
• What they did: A surface plasmon resonance screen identified LZ6; it increased Gal3BP engagement 3.4-fold, and in a four-arm factorial study of orthotopic GL261 tumors it was tested alone and with anti-PD-1.
• The result: LZ6 lowered CD206 and IL-10 and raised MHC class II and CD8 effector function, improving survival versus control (52.4 vs 26.3 days, P = 0.0012) and synergizing with anti-PD-1 (hazard ratio 0.24, 95% CI 0.10–0.57, P = 0.0014).