Fn14-scFv-granzyme B

Fn14-scFv-granzyme B (also known as GrB-Fc-IT4 or MRT-101) is a preclinical-stage recombinant fusion protein (immunotoxin) designed to target solid tumors overexpressing fibroblast growth factor-inducible 14 (Fn14, also known as TWEAK receptor or TNFRSF12A). Developed by the University of Texas MD Anderson Cancer Center in collaboration with the Clayton Foundation for Research and licensed to AbBC Therapies, the construct consists of a humanized single-chain antibody fragment (scFv) targeting Fn14 fused to human granzyme B, a pro-apoptotic serine protease, via an IgG Fc domain. Upon binding to Fn14 on the surface of tumor cells, the fusion protein is rapidly internalized via receptor-mediated endocytosis, delivering the granzyme B payload directly into the cytoplasm. Once inside, granzyme B bypasses the need for endosomal escape or linker cleavage to activate intracellular caspase cascades and induce mitochondrial depolarization, leading to rapid and irreversible apoptosis. Additionally, the drug has been shown to induce immunogenic cell death (ICD), triggering the release of damage-associated molecular patterns (DAMPs) such as HMGB1, ATP, and calreticulin, which can recruit and activate immune cells in the tumor microenvironment. Fn14-scFv-granzyme B has demonstrated potent, selective cytotoxicity in vitro and significant tumor growth inhibition in vivo across various solid tumor models, including triple-negative breast cancer (TNBC), colorectal cancer, and non-small cell lung cancer (NSCLC).

Other names

Fn14-scFv-GrBFn-14-scFv-GrBFn 14-scFv-GrBgranzyme B-Fc-IT4