Zhang Peng, Tao Changjuan, Shimura Takaya, Huang Andrew C, Kong Nana, Dai Yujie, Yao Shili, Xi Yun, Wang Xing, Fang Jianmin, Moses Marsha A, Guo Peng
Department of Medical Oncology, The Cancer Hospital of the University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, China.
Key Laboratory of Head and Neck Cancer Translational Research of Zhejiang Province, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, China.
iScience. 2023 Jul 3;26(8):107272. doi: 10.1016/j.isci.2023.107272. eCollection 2023 Aug 18.
Treatment options for anaplastic thyroid cancer (ATC) and refractory papillary thyroid carcinoma (PTC) are limited and outcomes remain poor. In this study, we determined via bioinformatic expression analyses and immunohistochemistry staining that intercellular adhesion molecule-1(ICAM1) is an attractive target for ATC and PTC. We designed and engineered two ICAM1-directed antibody-drug conjugate (I1-MMAE and I1-DXd), both of which potently and selectively ablate multiple human ATC and PTC cell lines without affecting non-plastic cells . Furthermore, I1-MMAE and I1-DXd mediated a potent tumor regression in ATC and PTC xenograft models. To develop a precision medicine, we also explored magnetic resonance imaging (MRI) as a non-invasive biomarker detection method to quantitatively map ICAM1 antigen expression in heterogeneous thyroid tumors. Taken together, this study provides a strong rationale for the further development of I1-MMAE and I1-DXd as promising therapeutic candidates to treat advanced PTC and ATC.
间变性甲状腺癌（ATC）和难治性乳头状甲状腺癌（PTC）的治疗选择有限，治疗效果仍然不佳。在本研究中，我们通过生物信息学表达分析和免疫组化染色确定，细胞间黏附分子-1（ICAM1）是ATC和PTC的一个有吸引力的靶点。我们设计并构建了两种靶向ICAM1的抗体-药物偶联物（I1-MMAE和I1-DXd），二者均能有效且选择性地消除多种人ATC和PTC细胞系，而不影响非肿瘤细胞。此外，I1-MMAE和I1-DXd在ATC和PTC异种移植模型中介导了显著的肿瘤消退。为了开发精准医学，我们还探索了磁共振成像（MRI）作为一种非侵入性生物标志物检测方法，以定量绘制异质性甲状腺肿瘤中ICAM1抗原的表达情况。综上所述，本研究为进一步开发I1-MMAE和I1-DXd作为治疗晚期PTC和ATC的有前景的治疗候选药物提供了有力的理论依据。
