G-M6Pn

G-M6Pn is a first-in-class lysosome-targeting chimera (LYTAC) designed to induce the degradation of extracellular and membrane-associated galectin-1 (Gal-1). Developed by researchers at Stanford University, including the Carolyn Bertozzi group, G-M6Pn is a bispecific molecule that simultaneously binds to Gal-1 and the cation-independent mannose-6-phosphate receptor (CI-M6PR). This dual binding shuttles Gal-1 into the endo-lysosomal pathway for degradation. Gal-1 is a known immunosuppressive protein overexpressed in various malignancies, including non-small cell lung cancer (NSCLC) and head and neck cancer (HNC), where it promotes T-cell apoptosis and regulatory T-cell expansion. By depleting Gal-1, G-M6Pn enhances anti-tumor immunity by activating CD8+ T cells and natural killer (NK) cells. Preclinical studies have demonstrated its efficacy in humanized mouse models, particularly when combined with stereotactic ablative radiotherapy, where it also appears to mediate an abscopal effect.