A High-Affinity Antibody-Drug Conjugates Actuximab-MMAE for Potent and Selective Targeting of CEACAM5-Positive Tumors

IF 9.1 1区医学 Q1 ONCOLOGY

Cancer letters Pub Date : 2025-03-29 DOI:10.1016/j.canlet.2025.217685

Yuqi Hu , Xin Du , Jiayu Yuan , Xizhao Gong , Yue Zhu , Hongde Li , Xiaorong Lin , Fang Zheng , Yuliang Ran , Zhenkun Na , Hai Hu

{"title":"A High-Affinity Antibody-Drug Conjugates Actuximab-MMAE for Potent and Selective Targeting of CEACAM5-Positive Tumors","authors":"Yuqi Hu , Xin Du , Jiayu Yuan , Xizhao Gong , Yue Zhu , Hongde Li , Xiaorong Lin , Fang Zheng , Yuliang Ran , Zhenkun Na , Hai Hu","doi":"10.1016/j.canlet.2025.217685","DOIUrl":null,"url":null,"abstract":"<div><div>Antibody-drug conjugates (ADCs) represent a promising class of anti-cancer therapy with an increasingly critical role in treating various tumors. They broaden the range of therapeutic targets, enabling the consideration of tumor-associated proteins that are overexpressed but lack well-defined mechanisms. Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) is a clinically relevant screening marker due to its tumor-specific overexpression, making it an attractive target for ADC development. However, the therapeutic potential of earlier anti-CEACAM5 ADCs has been limited by side effects and suboptimal drug-to-antibody ratios (DARs), restricting their clinical utility. In this study, we developed a novel anti-CEACAM5 ADC (named Actuximab-MMAE), characterized by high affinity, an optimized DAR, and potent tumor-selective cytotoxicity. Actuximab-MMAE demonstrated rapid and effective elimination of CEACAM5-positive tumors <em>in vivo</em> at low doses, while maintaining a favorable safety profile. These findings highlight Actuximab-MMAE as a promising therapeutic option for CEACAM5-overexpressing tumors, offering a new therapeutic method for targeted cancer therapy.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"620 ","pages":"Article 217685"},"PeriodicalIF":9.1000,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer letters","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0304383525002514","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Antibody-drug conjugates (ADCs) represent a promising class of anti-cancer therapy with an increasingly critical role in treating various tumors. They broaden the range of therapeutic targets, enabling the consideration of tumor-associated proteins that are overexpressed but lack well-defined mechanisms. Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) is a clinically relevant screening marker due to its tumor-specific overexpression, making it an attractive target for ADC development. However, the therapeutic potential of earlier anti-CEACAM5 ADCs has been limited by side effects and suboptimal drug-to-antibody ratios (DARs), restricting their clinical utility. In this study, we developed a novel anti-CEACAM5 ADC (named Actuximab-MMAE), characterized by high affinity, an optimized DAR, and potent tumor-selective cytotoxicity. Actuximab-MMAE demonstrated rapid and effective elimination of CEACAM5-positive tumors in vivo at low doses, while maintaining a favorable safety profile. These findings highlight Actuximab-MMAE as a promising therapeutic option for CEACAM5-overexpressing tumors, offering a new therapeutic method for targeted cancer therapy.

查看原文本刊更多论文

求助全文

约1分钟内获得全文求助全文

来源期刊

Cancer letters 医学-肿瘤学

CiteScore

17.70

自引率

2.10%

发文量

427

审稿时长

15 days

期刊介绍： Cancer Letters is a reputable international journal that serves as a platform for significant and original contributions in cancer research. The journal welcomes both full-length articles and Mini Reviews in the wide-ranging field of basic and translational oncology. Furthermore, it frequently presents Special Issues that shed light on current and topical areas in cancer research. Cancer Letters is highly interested in various fundamental aspects that can cater to a diverse readership. These areas include the molecular genetics and cell biology of cancer, radiation biology, molecular pathology, hormones and cancer, viral oncology, metastasis, and chemoprevention. The journal actively focuses on experimental therapeutics, particularly the advancement of targeted therapies for personalized cancer medicine, such as metronomic chemotherapy. By publishing groundbreaking research and promoting advancements in cancer treatments, Cancer Letters aims to actively contribute to the fight against cancer and the improvement of patient outcomes.