LRG1 Human

LRG1 consists of eight leucine-rich repeats, each mostly 20–30 amino acid residues in length . The gene encoding LRG1 is located on the short arm of chromosome 19, band 3, and region 13 (19P13.3) . The mature form of LRG1 is a secreted protein isolated from human serum, with a molecular weight of approximately 45 kDa . The amino acid sequence of LRG1 was determined in 1985, revealing 312 amino acids .

LRG1 plays a significant role in normal physiological activities, particularly in the nervous system. It is involved in synapse formation, synapse growth, the development of nerve processes, neurotransmitter transfer and release, and cell adhesion molecules or ligand-binding proteins . Additionally, LRG1 is a crucial upstream signaling molecule of transforming growth factor-beta (TGF-β), affecting various pathological processes through the TGF-β signaling pathway .

LRG1 is abundantly present in the microenvironment of many tumors, where it contributes to vascular dysfunction, impeding the delivery of therapeutics . It promotes pathological angiogenesis by corrupting the homeostatic influence of TGF-β signaling and interferes with vessel stabilization and maturation . This makes LRG1 a potential target for therapeutic interventions, particularly in cancer treatment .

Recent studies have focused on the development of novel therapeutic strategies targeting LRG1. For instance, a novel antibody-drug conjugate (ADC) comprising the anti-LRG1 hinge-stabilized IgG4 monoclonal antibody Magacizumab coupled to the anti-mitotic payload monomethyl auristatin E (MMAE) has shown promising results . This ADC retains binding post-modification, is stable in serum, and is effective in in vitro cell studies . Targeting LRG1 through this ADC has demonstrated increased survival in vivo compared to antibody alone and similar anti-tumor activity compared to standard chemotherapy, but without undesired side effects .