SIBP-03, a novel anti-HER3 antibody, exerts antitumor effects and synergizes with EGFR- and HER2-targeted drugs  

作　　者：Wen-jing Li Cheng-ying Xie Xi Zhu Jiao Tang Lei Wang Li-guang Lou 

机构地区：[1]Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai,201203,China [2]University of Chinese Academy of Sciences,Beijing,100049,China

出　　处：《Acta Pharmacologica Sinica》2024年第4期857-866,共10页中国药理学报（英文版）

基　　金：supported by grants from the Science and Technology Commission of Shanghai Municipality(No 18DZ2293200);the Yunnan Province Sciences and Technology plan(No 202102AA310026).

摘　　要：HER3 (human epidermal growth factor receptor 3) acts through heterodimerization with EGFR (epidermal growth factor receptor) or HER2 to play an essential role in activating phosphoinositide 3-kinase (PI3K) and AKT signaling—a crucial pathway that promotes tumor cell survival. HER3 is a promising target for cancer therapy, and several HER3-directed antibodies have already entered into clinical trials. In this study we characterized a novel anti-HER3 monoclonal antibody, SIBP-03. SIBP-03 (0.01−10 μg/mL) specifically and concentration-dependently blocked both neuregulin (NRG)-dependent and -independent HER3 activation, attenuated HER3-mediated downstream signaling and inhibited cell proliferation. This antitumor activity was dependent, at least in part, on SIBP-03–induced, cell-mediated cytotoxicity and cellular phagocytosis. Importantly, SIBP-03 enhanced the antitumor activity of EGFR- or HER2-targeted drugs (cetuximab or trastuzumab) in vitro and in vivo. The mechanisms underlying this synergy involve increased inhibition of HER3-mediated downstream signaling. Collectively, these results demonstrated that SIBP-03, which is currently undergoing a Phase I clinical trial in China, may offer a new treatment option for patients with cancers harboring activated HER3, particularly as part of a combinational therapeutic strategy.

关 键 词：SIBP-03 HER3 HER3-targeted therapy neuregulin 1 EGFR HER2 

分 类 号：R979.1[医药卫生—药品]