CST6N137D

CST6N137D is a recombinant mutant form of Cystatin E/M (CST6), a protease inhibitor being investigated for the treatment of multiple myeloma-induced bone disease. In multiple myeloma, wild-type CST6 is secreted by tumor cells and plays a dual role: it inhibits osteoclastogenesis, thereby preventing bone resorption and osteolytic lesions, but it also promotes an immunosuppressive microenvironment by upregulating PD-L1 on tumor-associated macrophages (TAMs) and inhibiting CD8+ T-cell proliferation. This immunosuppressive activity is linked to N-linked glycosylation at the N137 residue. CST6N137D is engineered with an asparagine-to-aspartic acid substitution at position 137, which prevents glycosylation. This modification allows the protein to retain its bone-protective protease inhibitory function while significantly reducing its immunosuppressive effects, making it a more suitable therapeutic candidate for managing bone disease in multiple myeloma patients without compromising anti-tumor immunity.

Other names

CST6 N137D mutantCST-6 N137D mutantCST 6 N137D mutantglycosylation-deficient CST6Cystatin E/M N137D mutant