ITEM4-rGel

ITEM4-rGel is an experimental immunotoxin composed of the monoclonal antibody ITEM-4, which targets the fibroblast growth factor-inducible 14 (Fn14) receptor, conjugated to recombinant gelonin (rGel). Fn14, also known as the TWEAK receptor, is a member of the TNF receptor superfamily that is highly overexpressed in various human solid tumors, including melanoma, breast, and pancreatic cancers, while showing minimal expression in normal tissues. The payload, rGel, is a Type I ribosome-inactivating protein (RIP) that functions as an N-glycosidase, specifically removing an adenine residue from the sarcin/ricin loop of the 28S rRNA. This action halts protein synthesis and induces apoptosis or necrosis in the target cell upon internalization. Developed by researchers at the M.D. Anderson Cancer Center and the University of Maryland, ITEM4-rGel has demonstrated potent, antigen-specific cytotoxicity and significant anti-tumor activity in preclinical models of melanoma and breast cancer.