中国科学院上海药物研究所楼丽广等研究人员合作发现新型抗HER3抗体SIBP-03与EGFR和HER2靶向药物协同发挥抗肿瘤作用。相关论文于2024年1月10日在线发表在《中国药理学报》上。

研究人员表示，HER3（人表皮生长因子受体3）通过与EGFR（表皮生长因子受体）或HER2异源二聚体发挥作用，在激活磷脂酰肌醇3-激酶（PI3K）和AKT信号（一条促进肿瘤细胞存活的重要途径）中扮演重要角色。HER3是一种很有前景的癌症治疗靶点，目前已有几种HER3靶向抗体进入临床试验阶段。

研究人员鉴定了一种新型抗HER3单克隆抗体SIBP-03。SIBP-03（0.01-10μg/mL）能特异性地、浓度依赖性地阻断神经调控素（NRG）依赖性和非依赖性的HER3活化，减弱HER3介导的下游信号传导，抑制细胞增殖。这种抗肿瘤活性至少部分依赖于SIBP-03诱导的细胞介导的细胞毒性和细胞吞噬作用。重要的是，SIBP-03增强了EGFR或HER2靶向药物（西妥昔单抗或曲妥珠单抗）在体外和体内的抗肿瘤活性。这种协同作用的机制涉及增加对HER3介导的下游信号传导的抑制。

总之，这些结果表明，目前正在中国进行一期临床试验的SIBP-03可为携带活化HER3的癌症患者提供一种新的治疗选择，尤其是作为联合治疗策略的一部分。

附：英文原文

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

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

Issue&Volume: 2024-01-10

Abstract: 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 (0.0110μg/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.

DOI: 10.1038/s41401-023-01221-4

Source: https://www.nature.com/articles/s41401-023-01221-4