anti-HER2 single-chain variable fragment-granzyme b fusion protein

The anti-HER2 single-chain variable fragment-granzyme b fusion protein, also known as immunoGrB, is a recombinant biologic therapeutic designed to target and eliminate HER2-overexpressing cancer cells. It is a chimeric protein comprising three functional domains: an anti-HER2 single-chain variable fragment (scFv) for high-affinity tumor targeting, a translocation domain derived from Pseudomonas exotoxin A (ETA') to facilitate cytosolic entry, and human granzyme B as the cytotoxic effector. Upon binding to HER2 on the cell surface, the fusion protein is internalized via endocytosis. The ETA' domain then enables the escape of granzyme B into the cytoplasm, where it induces apoptosis through both caspase-dependent and caspase-independent pathways. Beyond direct cytotoxicity, the drug is designed to trigger immunogenic cell death (ICD), characterized by the release of damage-associated molecular patterns (DAMPs) such as HMGB1, ATP, and Calreticulin, which can stimulate a secondary anti-tumor immune response. Developed by the Clayton Foundation for Research and investigators at MD Anderson Cancer Center, this agent is being investigated for its potential in treating HER2-positive malignancies, including breast and ovarian cancers, particularly those resistant to standard apoptotic triggers.

Other names

anti-HER2 scFv-GrBanti-HER-2 scFv-GrBanti-HER 2 scFv-GrBscFv-GrB-ETA'anti-HER2-ETA'-GrB