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huE22-AcBut-CM is an investigational **EFNA4-targeted antibody-drug conjugate** built from the humanized anti-ephrin-A4 monoclonal antibody huE22 linked through **4-(4-acetylphenoxy)butanoic acid** to **N-acetyl-gamma-calicheamicin dimethyl hydrazide**. The antibody component binds **ephrin-A4**, an internalizing cell-surface ligand overexpressed in subsets of solid tumors and tumor-initiating cell populations, especially in triple-negative breast cancer and also in ovarian, lung, colorectal, and hepatocellular tumors. After target binding and internalization, the acid-labile linker enables intracellular release of the calicheamicin payload, producing DNA double-strand breaks, gamma-H2A.X induction, apoptosis, and tumor cell killing. In preclinical studies described in the supplied patent material, huE22-AcBut-CM showed potent and selective in vitro cytotoxicity and strong in vivo activity in EFNA4-positive patient-derived xenograft models, including durable regressions in triple-negative breast and ovarian cancer models, with evidence of reducing tumor-initiating cell frequency. The program appears to be a preclinical asset originating from EFNA4 antibody-drug conjugate work disclosed in patent filings rather than a marketed medicine.
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