M4-3-ML2

M4-3-ML2 is a glycoengineered, humanized IgG1 monoclonal antibody targeting the membrane-proximal D3 domain of melanoma-associated chondroitin sulfate proteoglycan (MCSP), also known as CSPG4. Developed by Roche using its proprietary GlycoMab technology, M4-3-ML2 is designed to enhance binding affinity for the FcγRIIIa receptor on natural killer (NK) cells, thereby significantly boosting antibody-dependent cellular cytotoxicity (ADCC) against tumor cells. MCSP is a large transmembrane proteoglycan highly expressed in 60-80% of melanomas, as well as in other solid tumors like glioblastoma and breast carcinoma, and on the pericytes of tumor neovasculature. In preclinical studies, M4-3-ML2 demonstrated potent anti-tumor activity and improved survival in disseminated melanoma xenograft models, outperforming non-glycoengineered parental antibodies.