结直肠癌
抗体-药物偶联物
癌症研究
医学
癌症
抗体
免疫疗法
刺
癌细胞
细胞毒性T细胞
免疫学
内科学
体外
单克隆抗体
生物
生物化学
工程类
航空航天工程
作者
Xiaohan Wu,Lingyan Xu,Xiaofei Li,Yubin Zhou,Xiao Han,Wei Zhang,Weicheng Wang,Wenjie Guo,Wen Li,Qiang Xu,Yanhong Gu
标识
DOI:10.1038/s41419-023-06073-8
摘要
Human epidermal growth factor receptor 2 (HER2) is a protein that is overexpressed in some types of cancer, including breast and urothelial cancer. Here we found that HER2 was present in a portion of colon cancer patients, raising the possibility of using anti-HER2 therapy. RC48, a novel antibody-drug conjugate (ADC) comprising cytotoxic monomethyl auristatin E (MMAE) and an anti-HER2 antibody tethered via a linker, showed a comparable therapeutic effect in both HER2 low expressed (IHC2+/FISH- or IHC+) and high expressed urothelial cancer patients. In vitro studies using colon cancer cell lines showed that RC48 effectively impeded the proliferation of HER2-positive cells, indicating its potential as a treatment for HER2-positive colon cancer. Mechanism study showed that RC48 not only induces cell cycle arrest but also disrupts HER2-mediated restain of cGAS-STING signaling, potentially activating an immune response against the cancer cells. The administration of RC48 significantly reduced the growth of HER2-positive colon cancer and made HER2-positive colon cancer cells more susceptible to immunotherapy. The results of our study will contribute to determining the feasibility of RC48 as a therapeutic option for HER2-positive colon cancer.
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