Tumor-targeting anti-EGFR x anti-PD1 bispecific antibody inhibits EGFR-overexpressing tumor growth by combining EGFR blockade and immune activation with direct tumor cell killing.

Abstract

We developed a strategy to combine conventional targeted therapy with immune checkpoint blockade using a tumor-targeting bispecific antibody (BsAb) to treat solid tumors. The BsAb was designed to simultaneously engage a tumor-associated antigen, epidermal growth factor receptor (EGFR), and programed cell death protein 1 (PD1). In addition to its direct anti-tumor activity via EGFR inhibition, the BsAb mediated efficient antibody-dependent cellular cytotoxicity (ADCC) and activated T cell antitumor im munity through blockade of PD1 from interacting with its counterpart, programed cell death ligand 1 (PDL1). Further, the BsAb exhibited a potent direct tumor cell killing activity in the presence of PBMC, most likely, via activating and, at the same time, physically engaging T cells with tumor cells. Taken together, we here illustrate a new strategy in the design and production of novel BsAbs with enhanced therapeutic efficacy through both direct tumor growth inhibition and T cell activation via tumor-targeted immune checkpoint blockade.

• Authors: Li Li, Lan Deng, Xiaoqing Meng, Changling Gu, Li Meng, Kai Li, Xuesai Zhang, Yun Meng, Wei Xu, Le Zhao, Jianhe Chen, Zhenping Zhu, Haomin Huang
• Journal: Translational oncology (Transl Oncol) Vol. 14 Issue 1 Pg. 100916 (Jan 2021) ISSN: 1936-5233 [Print] United States
• PMID: 33129108 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.