Anti-Human TROP2 Monoclonal Antibody (Datopotamab)

TROP2 (Trophoblast Cell Surface Antigen 2), also known as GA733-1 or EGP-1, is a type I transmembrane glycoprotein belonging to the TACSTD gene family that is highly expressed in various epithelial cancers, including triple-negative breast cancer, lung adenocarcinoma, urothelial carcinoma, and gastric cancer, while showing limited expression in normal tissues. Structurally, it features an extracellular domain with a thyroglobulin type-1 repeat and a phosphodiesterase domain, a single transmembrane helix, and a short cytoplasmic tail containing a PIP2-binding site and PKC phosphorylation sites. TROP2 plays critical roles in tumor progression by regulating intracellular calcium signaling, cell proliferation, migration, and survival through its interaction with IGF-1R and FAK signaling pathways, and its ability to undergo regulated intramembrane proteolysis (RIP) releases an intracellular domain (ICD) that translocates to the nucleus to modulate gene expression. Due to its tumor-selective overexpression and internalization properties upon ligand binding, TROP2 has emerged as a promising therapeutic target, most notably through antibody-drug conjugates (ADCs) such as sacituzumab govitecan (Trodelvy), which received FDA approval for metastatic triple-negative breast cancer and urothelial cancer, demonstrating significant clinical efficacy by delivering cytotoxic payloads directly to TROP2-expressing tumor cells while sparing normal tissues.