CTX-CNF1

CTX-CNF1 is a novel brain-penetrant recombinant fusion protein developed by the Consiglio Nazionale delle Ricerche (CNR) and the Scuola Normale Superiore di Pisa for the treatment of glioblastoma. The chimeric protein combines chlorotoxin (CTX), a 36-amino acid peptide derived from scorpion venom that crosses the blood-brain barrier and selectively targets glioma cells, with cytotoxic necrotizing factor 1 (CNF1), an Escherichia coli-derived bacterial toxin. Mechanistically, CTX-CNF1 binds to glioma-associated targets such as matrix metalloproteinase-2 (MMP-2), chloride voltage-gated channel 3 (CLCN3), and annexin A2 via its CTX domain, facilitating selective tumor targeting and internalization. Once inside the cell, the CNF1 domain binds to the basal cell adhesion molecule (BCAM) receptor and deamidates Rho GTPases (RhoA, Rac1, and Cdc42), leading to their constitutive activation. This dual-action mechanism impairs glioma cell proliferation, induces senescence, and remodels the immunosuppressive tumor microenvironment by promoting pro-inflammatory reprogramming of tumor-associated macrophages and enhancing CD8+ T-cell infiltration.

Other names

chlorotoxin-cytotoxic necrotizing factor 1 fusion proteinchlorotoxin-cytotoxic necrotizing factor 1 recombinant protein