Characterization of mAb104, a mAb Targeting a Conformationally Exposed, Tumor-Specific Epitope of HER2

Abstract

We generated a novel HER2 mAb104, which binds to an epitope in domain II of HER2 that is conformationally exposed in tumors in response to HER2 amplification or activation but is not accessible to antibody binding in normal tissues. Consistent with other studies that evaluated antibodies targeting conformationally exposed epitopes, mAb104 lacked in vitro activity but showed potent antitumor activity in vivo. The antitumor effect in vivo was similar in magnitude to trastuzumab and pertuzumab, and combination with trastuzumab was superior to trastuzumab alone. IHC screening of normal and tumor tissues with mAb104 showed that mAb104 did not bind to normal tissues, confirming the tumor specifici..