An antibody-drug conjugate for endometrioid carcinoma based on the expression of cell adhesion molecule 1.

IF 2.6 Q3 ONCOLOGY

Molecular and Cellular Oncology Pub Date : 2024-09-05 eCollection Date: 2024-01-01 DOI:10.1080/23723556.2024.2399379

Man Hagiyama, Azusa Yoneshige, Tomoyuki Otani, Akihiro Wada, Fuka Takeuchi, Yuji Shoya, Takao Inoue, Akihiko Ito

{"title":"An antibody-drug conjugate for endometrioid carcinoma based on the expression of cell adhesion molecule 1.","authors":"Man Hagiyama, Azusa Yoneshige, Tomoyuki Otani, Akihiro Wada, Fuka Takeuchi, Yuji Shoya, Takao Inoue, Akihiko Ito","doi":"10.1080/23723556.2024.2399379","DOIUrl":null,"url":null,"abstract":"Cell adhesion molecule 1 (CADM1), an immunoglobulin superfamily member, is expressed in endometrial glandular cells highly during the proliferative phase but lowly during the secretory phase. Previously, a CADM1-targeting antibody-drug conjugate (ADC) was generated, in which a humanized anti-CADM1 ectodomain antibody h3E1 was linked with monomethyl auristatin E (h3E1-MMAE ADC). The present study aimed at probing whether this ADC could be useful for the treatment of endometrial neoplasm. Firstly, immunohistochemistry for CADM1 was conducted on proliferative-phase endometrium (n = 13), endometrial hyperplasia (n = 35), and endometrioid carcinoma at various stages (n = 166). CADM1 immunostaining intensity was highest in atypical endometrial hyperplasia and endometrioid carcinoma confined within the endometrium and was decreased stepwise as the carcinoma stage progressed. Next, h3E1-MMAE ADC was examined for its cytotoxicity in vitro using human endometrial adenocarcinoma cell lines expressing CADM1; HEC-1B, HEC-50B, JHUM-3, and OMC-2. The ADC killed these cells in a dose-dependent manner with half maximal inhibitory concentration (IC50) of 12.02 nM for HEC-1B and 2.04 nM for HEC-50B. Collectively, h3E1-MMAE ADC may serve as a noninvasive alternative to simple hysterectomy in the treatment of endometrioid carcinoma confined within the endometrium.","PeriodicalId":37292,"journal":{"name":"Molecular and Cellular Oncology","volume":"11 1","pages":"2399379"},"PeriodicalIF":2.6000,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11382700/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular and Cellular Oncology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1080/23723556.2024.2399379","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q3","JCRName":"ONCOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Cell adhesion molecule 1 (CADM1), an immunoglobulin superfamily member, is expressed in endometrial glandular cells highly during the proliferative phase but lowly during the secretory phase. Previously, a CADM1-targeting antibody-drug conjugate (ADC) was generated, in which a humanized anti-CADM1 ectodomain antibody h3E1 was linked with monomethyl auristatin E (h3E1-MMAE ADC). The present study aimed at probing whether this ADC could be useful for the treatment of endometrial neoplasm. Firstly, immunohistochemistry for CADM1 was conducted on proliferative-phase endometrium (n = 13), endometrial hyperplasia (n = 35), and endometrioid carcinoma at various stages (n = 166). CADM1 immunostaining intensity was highest in atypical endometrial hyperplasia and endometrioid carcinoma confined within the endometrium and was decreased stepwise as the carcinoma stage progressed. Next, h3E1-MMAE ADC was examined for its cytotoxicity in vitro using human endometrial adenocarcinoma cell lines expressing CADM1; HEC-1B, HEC-50B, JHUM-3, and OMC-2. The ADC killed these cells in a dose-dependent manner with half maximal inhibitory concentration (IC50) of 12.02 nM for HEC-1B and 2.04 nM for HEC-50B. Collectively, h3E1-MMAE ADC may serve as a noninvasive alternative to simple hysterectomy in the treatment of endometrioid carcinoma confined within the endometrium.

查看原文本刊更多论文

基于细胞粘附分子 1 表达的子宫内膜样癌抗体-药物共轭物。

细胞粘附分子 1（CADM1）是一种免疫球蛋白超家族成员，在子宫内膜腺细胞的增殖期高表达，而在分泌期低表达。此前，一种人源化的抗 CADM1 外域抗体 h3E1 与单甲基乌司他丁 E（h3E1-MMAE ADC）结合，生成了一种 CADM1 靶向抗体-药物共轭物（ADC）。本研究旨在探讨这种 ADC 是否可用于治疗子宫内膜肿瘤。首先，对增殖期子宫内膜（13 例）、子宫内膜增生症（35 例）和不同阶段的子宫内膜样癌（166 例）进行了 CADM1 免疫组化。在非典型子宫内膜增生和局限于子宫内膜的子宫内膜样癌中，CADM1 免疫染色强度最高，随着癌阶段的进展，CADM1 免疫染色强度逐渐降低。接着，使用表达 CADM1 的人类子宫内膜腺癌细胞系 HEC-1B、HEC-50B、JHUM-3 和 OMC-2 对 h3E1-MMAE ADC 的细胞毒性进行了体外检测。ADC 能以剂量依赖的方式杀死这些细胞，对 HEC-1B 和 HEC-50B 的半数最大抑制浓度（IC50）分别为 12.02 nM 和 2.04 nM。总之，在治疗局限于子宫内膜的子宫内膜样癌时，h3E1-MMAE ADC 可作为简单子宫切除术的非侵入性替代疗法。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Molecular and Cellular Oncology Biochemistry, Genetics and Molecular Biology-Cancer Research

CiteScore

3.20

自引率

0.00%

发文量

期刊介绍： For a long time, solid neoplasms have been viewed as relatively homogeneous entities composed for the most part of malignant cells. It is now clear that tumors are highly heterogeneous structures that evolve in the context of intimate interactions between cancer cells and endothelial, stromal as well as immune cells. During the past few years, experimental and clinical oncologists have witnessed several conceptual transitions of this type. Molecular and Cellular Oncology (MCO) emerges within this conceptual framework as a high-profile forum for the publication of fundamental, translational and clinical research on cancer. The scope of MCO is broad. Submissions dealing with all aspects of oncogenesis, tumor progression and response to therapy will be welcome, irrespective of whether they focus on solid or hematological neoplasms. MCO has gathered leading scientists with expertise in multiple areas of cancer research and other fields of investigation to constitute a large, interdisciplinary, Editorial Board that will ensure the quality of articles accepted for publication. MCO will publish Original Research Articles, Brief Reports, Reviews, Short Reviews, Commentaries, Author Views (auto-commentaries) and Meeting Reports dealing with all aspects of cancer research.