State Key Laboratory of Military Stomatology, Department of General Dentistry and Emergency, School of Stomatology, Air Force Military Medical University, Xi'an, China.
School of Stomatology of Qingdao University, Qingdao, China.
Drug Deliv. 2022 Dec;29(1):1335-1344. doi: 10.1080/10717544.2022.2069883.
Human epidermal growth factor receptor 2 (HER2) regulates cell mitosis, proliferation, and apoptosis. Trastuzumab is a HER2-targeted monoclonal antibody (mAB), which can prolong the overall survival rate of patients with HER2 overexpression in later periods of gastric cancer and breast cancer. Although anti-HER2 monoclonal antibody has a curative effect, adjuvant chemotherapy is still necessary to upgrade the curative effect maximumly. Antibody-drug conjugate (ADC) is a kind of therapeutic drug that contains antigen-specific antibody and cytotoxic payload, which can improve the survival time of tumor patients. To date, there are several HER2-ADC products on the market, for which two anti-HER2 ADC (trastuzumab emtansine and trastuzumab deruxtecan) have been authorized by the FDA for distinct types of HER2-positive carcinoma in the breast. Disitamab vedotin (RC48) is a newly developed ADC drug targeting HER2 that is comprised of hertuzumab coupling monomethyl auristatin E (MMAE) via a cleavable linker. This paper aims to offer a general insight and summary of the mechanism of action and the currently completed and ongoing clinical studies of RC-48 in HER-2 positive solid tumors.
人表皮生长因子受体 2(HER2)调节细胞有丝分裂、增殖和凋亡。曲妥珠单抗是一种 HER2 靶向的单克隆抗体(mAB),可延长 HER2 过表达的胃癌和乳腺癌患者的总生存率。尽管抗 HER2 单克隆抗体有疗效,但仍需辅助化疗以最大限度地提高疗效。抗体药物偶联物(ADC)是一种含有抗原特异性抗体和细胞毒性有效载荷的治疗药物,可改善肿瘤患者的生存时间。迄今为止,已有多种 HER2-ADC 产品上市,其中两种抗 HER2 ADC(曲妥珠单抗emtansine 和 trastuzumab deruxtecan)已被 FDA 批准用于不同类型的 HER2 阳性乳腺癌。Disitamab vedotin(RC48)是一种新开发的靶向 HER2 的 ADC 药物,它由 hertuzumab 通过可裂解的连接子偶联单甲基澳瑞他汀 E(MMAE)组成。本文旨在对 RC-48 在 HER-2 阳性实体瘤中的作用机制及目前已完成和正在进行的临床研究进行综述。