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HER2-Affitoxin is a novel recombinant fusion toxin protein therapy developed by the National Cancer Institute (NCI) for the treatment of HER2-overexpressing cancers, including breast, ovarian, and gastric cancers. The molecule is composed of a HER2-specific Affibody targeting moiety genetically fused to a truncated and optimized version of Pseudomonas aeruginosa exotoxin A (PE38KDEL). Upon binding to HER2 on the surface of cancer cells, HER2-Affitoxin is internalized and delivered to the cytosol, where the toxin moiety catalyzes the ADP-ribosylation of eukaryotic translation elongation factor 2 (eEF2). This action halts protein synthesis and induces apoptosis in the target cells. Preclinical studies have demonstrated that HER2-Affitoxin is highly potent in vitro and can eradicate HER2-positive tumor xenografts in mouse models.
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