MINI REVIEW article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1678907
This article is part of the Research TopicThe Insights of Multi-Omics into the Microenvironment After Tumor Metastasis: A Paradigm Shift in Molecular Targeting Modeling and Immunotherapy for Advanced Cancer PatientsView all 21 articles
Antibody-Drug Conjugates as Immuno-Oncology Agents in Colorectal Cancer: Targets, Payloads, and Therapeutic Synergies
Provisionally accepted
- 1China-Japan Union Hospital of Jilin University Department of Gastrointestinal and Colorectal Surgery, Changchun, China
- 2Department of Thoracic Surgery, Jiangmen Central Hospital, Jiangmen, China
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Colorectal cancer (CRC), particularly the immunologically “cold” microsatellite-stable (MSS) subtype, remains profoundly resistant to immune checkpoint inhibitors. Antibody-drug conjugates (ADCs) are rapidly emerging as a transformative therapeutic modality poised to overcome this challenge. This review reframes ADCs beyond their role as targeted cytotoxics, repositioning them as sophisticated immuno-oncology agents. The central thesis is that by strategically selecting payloads such as topoisomerase inhibitors or auristatins, modern ADCs can induce immunogenic cell death (ICD) or pyroptosis. This mechanism effectively functions as an in situ vaccine, transforming the tumor microenvironment from “cold” to “hot” by promoting dendritic cell activation and T-cell infiltration. We provide a comprehensive overview of the ADC landscape, examining key targets on bulk tumor cells (CEACAM5, HER2), cancer stem cells (LGR5, GPR56), and stromal components. We conclude that the future of ADCs in CRC lies in their rational application as immune-priming agents, creating powerful synergies in combination with checkpoint inhibitors to break therapeutic resistance and durably improve patient outcomes.
Keywords: colorectal cancer, microsatellite stable, Antibody-drug conjugate, Immunoconjugate, ADC, immuno-oncology
Received: 03 Aug 2025; Accepted: 14 Oct 2025.
Copyright: © 2025 Wang, Lu, Xu, Xu, Chu and Fang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Shengshan Xu, xushengshan97@163.com
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