2. Academic Validation
  3. A high-affinity antibody-drug conjugates Actuximab-MMAE for potent and selective targeting of CEACAM5-Positive tumors

A high-affinity antibody-drug conjugates Actuximab-MMAE for potent and selective targeting of CEACAM5-Positive tumors

  • Cancer Lett. 2025 Jun 28:620:217685. doi: 10.1016/j.canlet.2025.217685.
Yuqi Hu 1,  Xin Du 2,  Jiayu Yuan 3,  Xizhao Gong 3,  Yue Zhu 3,  Hongde Li 4,  Xiaorong Lin 5,  Fang Zheng 1,  Yuliang Ran 6,  Zhenkun Na 7,  Hai Hu 8
Affiliations

Affiliations

  • 1 Department of Oncology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China.
  • 2 Breast Cancer Center, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine, Chinese Academy of Sciences, Hangzhou, 310022, China.
  • 3 Postgraduate Training Base Alliance of Wenzhou Medical University, Zhejiang Cancer Hospital, Hangzhou, 310022, China.
  • 4 Hangzhou Institute of Medicine, Chinese Academy of Sciences, Zhejiang Cancer Hospital, Hangzhou, 310018, China.
  • 5 Diagnosis and Treatment Center of Breast Diseases, Shantou Central Hospital, Shantou, 515000, China.
  • 6 State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China. Electronic address: ranyuliang@cicams.ac.cn.
  • 7 Hangzhou Institute of Medicine, Chinese Academy of Sciences, Zhejiang Cancer Hospital, Hangzhou, 310018, China. Electronic address: nazhenkun@him.cas.cn.
  • 8 Breast Cancer Center, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine, Chinese Academy of Sciences, Hangzhou, 310022, China; Postgraduate Training Base Alliance of Wenzhou Medical University, Zhejiang Cancer Hospital, Hangzhou, 310022, China; Hangzhou Institute of Medicine, Chinese Academy of Sciences, Zhejiang Cancer Hospital, Hangzhou, 310018, China. Electronic address: huhai@zjcc.org.cn.
PMID: 40158720 DOI: 10.1016/j.canlet.2025.217685
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.

Keywords

Antibody-drug conjugate; Carcinoembryonic antigen-related cell adhesion molecules 5; Colorectal carcinoma; Drug-antibody ratio; Solid tumor.

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