MEDI3185 has picomolar binding affinity to human CXCR4 and exhibits no significant binding to other chemokine receptors such as CCR4 or CXCR3. In vitro studies demonstrated that MEDI3185 inhibited tumor cell migration, blocked SDF-1 induced tumor cell signaling, and induced apoptosis of tumor cells. The MEDI3185 epitope comprises the entire ECL2 sequence, lacks any so-called 'hot-spot, ' and is remarkably resistant to mutations. The structure of MEDI3185 variable domains was modeled and suggested a β-strand/β-strand interaction between MEDI3185 CDR3H and CXCR4 ECL2, resulting in direct steric hindrance with CXCR4 ligand SDF-1.