An anti-TROP2 monoclonal antibody TrMab-6 exerts antitumor activity in breast cancer mouse xenograft models
An anti-TROP2 monoclonal antibody TrMab-6 exerts antitumor activity in breast cancer mouse xenograft models
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DOI：
10.3892/or.2021.8083
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发表时间：
2021-07-01
期刊：
影响因子：
4.2
通讯作者：
Kato, Yukinari
中科院分区：
文献类型：
--
作者：
Tanaka, Tomohiro;Ohishi, Tomokazu;Kato, Yukinari
据报道，滋养层细胞表面抗原2（TROP 2）在几种类型的癌症中过表达，其参与许多类型的癌症的细胞增殖、侵袭、转移和不良预后。先前，使用基于细胞的免疫和筛选（CBIS）方法开发了高灵敏度的抗TR 0 P2单克隆抗体（克隆TrMab-6;小鼠IgG（2b），κ）。TrMab-6可用于使用流式细胞术、蛋白质印迹和免疫组织化学的研究。本研究的目的是使用TROP 2过表达的CHO-K1（CHO/TROP 2）和乳腺癌细胞系（包括MCF 7、MDA-MB-231和MDA-MB-468）的小鼠异种移植模型，研究TrMab-6是否具有体外抗体依赖性细胞毒性（ADCC）或补体依赖性细胞毒性（CDC）活性或体内抗肿瘤活性。体外实验显示，TrMab-6强烈诱导针对CHO/TROP 2和三种乳腺癌细胞系的ADCC和CDC活性，而其未显示针对亲本CHO-K1和MCF 7/TROP 2敲除细胞的那些活性。此外，对CHO/TR 0 P2和MCF 7异种移植物的体内实验显示，TrMab-6显著降低肿瘤生长，而其对亲本CHO-Kl和MCF 7/TR 0 P2敲除异种移植物未显示抗肿瘤活性。研究结果表明，TrMab-6是TROP 2表达乳腺癌的一种有希望的治疗选择。
Trophoblast cell surface antigen 2 (TROP2), reported to be overexpressed in several types of cancer, is involved in cell proliferation, invasion, metastasis, and poor prognosis of many types of cancer. Previously, a highly sensitive anti-TROP2 monoclonal antibody (clone TrMab-6; mouse IgG(2b), kappa) was developed using a Cell-Based Immunization and Screening (CBIS) method. TrMab-6 was useful for investigations using flow cytometry, western blot, and immunohistochemistry. The aim of the present study was to investigate whether TrMab-6 possesses in vitro antibody-dependent cellular cytotoxicity (ADCC) or complement-dependent cytotoxicity (CDC) activities or in vivo antitumor activities using mouse xenograft models of TROP2-overexpressed CHO-K1 (CHO/TROP2) and breast cancer cell lines, including MCF7, MDA-MB-231, and MDA-MB-468. In vitro experiments revealed that TrMab-6 strongly induced ADCC and CDC activities against CHO/TROP2 and the three breast cancer cell lines, whereas it did not show those activities against parental CHO-K1 and MCF7/TROP2-knockout cells. Furthermore, in vivo experiments on CHO/TROP2 and MCF7 xenografts revealed that TrMab-6 significantly reduced tumor growth, whereas it did not show antitumor activities against parental CHO-K1 and MCF7/TROP2-knockout xenografts. The findings suggest that TrMab-6 is a promising treatment option for TROP2-expressing breast cancers.