Blockade of ErbB2 and PD-L1 using a bispecific antibody to improve targeted anti-ErbB2 therapy.

ABSTRACT: A significant proportion of human epidermal growth factor receptor 2 (Her2/ErbB2)-positive metastatic breast cancer patients are refractory to Her2-targeted trastuzumab-like therapy. Some of this resistance has been attributed to the upregulation of immune checkpoints such as programmed cell death-1 (PD-1) and its ligand, PD-L1 in Her2-positive breast cancer patients. Therefore, therapies targeting both the PD-1/PD-L1 interaction and oncogenic Her2 signaling are of significant clinical interest. Here, we constructed a mouse bispecific antibody targeting PD-L1 and rat Her2 (referred to as BsPD-L1xrErbB2) aiming to redirect the anti-PD-L1 response toward Her2-expressing tumor cells. BsPD-L1xrErbB2 demonstrated additive binding to interferon (IFN)-γ treated Her2⁺ TUBO tumor cells,

SUBMITTER: Mittal D 

PROVIDER: S-EPMC6791437 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature