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抗 TROP2 单克隆抗体 TrMab-6 在乳腺癌小鼠异种移植模型中发挥抗肿瘤活性。

An anti‑TROP2 monoclonal antibody TrMab‑6 exerts antitumor activity in breast cancer mouse xenograft models.

机构信息

Department of Antibody Drug Development, Tohoku University Graduate School of Medicine, Aoba‑ku, Sendai, Miyagi 980‑8575, Japan.

Institute of Microbial Chemistry (BIKAKEN), Numazu, Microbial Chemistry Research Foundation, Numazu‑shi, Shizuoka 410‑0301, Japan.

出版信息

Oncol Rep. 2021 Jul;46(1). doi: 10.3892/or.2021.8083. Epub 2021 May 20.

DOI:10.3892/or.2021.8083
PMID:34013368
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8144932/
Abstract

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, κ) 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 antibody‑dependent cellular cytotoxicity (ADCC) or complement‑dependent cytotoxicity (CDC) activities or 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. 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, 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.

摘要

滋养层细胞表面抗原 2(TROP2)在多种类型的癌症中表达过度,参与多种类型癌症的细胞增殖、侵袭、转移和预后不良。先前,使用基于细胞的免疫接种和筛选(CBIS)方法开发了一种高灵敏度的抗 TROP2 单克隆抗体(克隆 TrMab-6;鼠 IgG,κ)。TrMab-6 可用于流式细胞术、western blot 和免疫组织化学研究。本研究旨在探讨 TrMab-6 是否具有抗体依赖性细胞毒性(ADCC)或补体依赖性细胞毒性(CDC)活性或抗肿瘤活性,使用 TROP2 过表达 CHO-K1(CHO/TROP2)和乳腺癌细胞系(包括 MCF7、MDA-MB-231 和 MDA-MB-468)的小鼠异种移植模型进行研究。体外实验表明,TrMab-6 强烈诱导 ADCC 和 CDC 活性,针对 CHO/TROP2 和三种乳腺癌细胞系,而对亲本 CHO-K1 和 MCF7/TROP2 敲除细胞没有这些活性。此外,CHO/TROP2 和 MCF7 异种移植实验表明,TrMab-6 显著降低肿瘤生长,而对亲本 CHO-K1 和 MCF7/TROP2 敲除异种移植没有抗肿瘤活性。这些发现表明,TrMab-6 是一种有前途的治疗 TROP2 表达型乳腺癌的选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c3d/8144932/6881ae0610d1/or-46-01-8083-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c3d/8144932/4ce8b9d9b65d/or-46-01-8083-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c3d/8144932/a805facd125d/or-46-01-8083-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c3d/8144932/fec446e0a506/or-46-01-8083-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c3d/8144932/6416c4abefa7/or-46-01-8083-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c3d/8144932/6881ae0610d1/or-46-01-8083-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c3d/8144932/4ce8b9d9b65d/or-46-01-8083-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c3d/8144932/a805facd125d/or-46-01-8083-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c3d/8144932/fec446e0a506/or-46-01-8083-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c3d/8144932/6416c4abefa7/or-46-01-8083-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c3d/8144932/6881ae0610d1/or-46-01-8083-g04.jpg

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