To determine whether the improved target selectivity seen in vitro could be exploited to enhance functional selectivity in physiological settings, we tested the ability of the affinity-modulated DuetMab variants to selectively target and eradicate double-positive NCI-H358 tumors over single-positive NCI-H358.HER2.ko tumors in nude mice bearing dual-flank tumor xenografts. Here, ERBB2 is linked to neoplasm.