The DOI matches its Crossref record; 248 of the 248 references it cites were found in a registry or an index.
Exploring the next generation of antibody–drug conjugates
Abstract
Antibody-drug conjugates (ADCs) are a promising cancer treatment modality that enables the selective delivery of highly cytotoxic payloads to tumours. However, realizing the full potential of this platform necessitates innovative molecular designs to tackle several clinical challenges such as drug resistance, tumour heterogeneity and treatment-related adverse effects. Several emerging ADC formats exist, including bispecific ADCs, conditionally active ADCs (also known as probody-drug conjugates), immune-stimulating ADCs, protein-degrader ADCs and dual-drug ADCs, and each offers unique capabilities for tackling these various challenges. For example, probody-drug conjugates can enhance tumour specificity, whereas bispecific ADCs and dual-drug ADCs can address resistance and heterogeneity with enhanced activity. The incorporation of immune-stimulating and protein-degrader ADCs, which have distinct mechanisms of action, into existing treatment strategies could enable multimodal cancer treatment. Despite the promising outlook, the importance of patient stratification and biomarker identification cannot be overstated for these emerging ADCs, as these factors are crucial to identify patients who are most likely to derive benefit. As we continue to deepen our understanding of tumour biology and refine ADC design, we will edge closer to developing truly effective and safe ADCs for patients with treatment-refractory cancers. In this Review, we highlight advances in each ADC component (the monoclonal antibody, payload, linker and conjugation chemistry) and provide more-detailed discussions on selected examples of emerging novel ADCs of each format, enabled by engineering of one or more of these components.
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“Thirteen FDA-approved ADCs are currently on the market, with over 200 ADCs in various stages of clinical development (Table 1)6,8,9.”
From The evolving landscape of antibody-drug conjugates (ADCs) for treatment of prostate cancer (2025) · cites this paper as [8]
In the citing paper
“To date, 11 ADCs have been Food and Drug Administration (FDA)-approved for 20 specific indications”
From Current and emerging concepts for systemic treatment of metastatic colorectal cancer (2025) · cites this paper as [59]
Citations
Cites
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Strategies and challenges for the next generation of antibody–drug conjugates
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Blinatumomab versus Chemotherapy for Advanced Acute Lymphoblastic Leukemia
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Site-specific conjugation of a cytotoxic drug to an antibody improves the therapeutic index
Junutula, J. R., Raab, H. E., Clark, S., Bhakta, S., Leipold, D. D., Weir, S., Chen, Y., Simpson, M., Tsai, S. P., Dennis, M. S., et al. (2008) · Nature Biotechnology · doi:10.1038/nbt.1480 · Cited by 1,388
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Unlocking the potential of antibody–drug conjugates for cancer therapy
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Research works printed but not linked: 1
- CytomX Therapeutics Inc. CytomX therapeutics presents overview of conditionally-activated antibody-drug conjugate (ADC) programs including next generation EpCAM-targeting CX-2051. CytomX Press Release Details https://ir.cytomx.com/news-releases/news-release-details/cytomx-therapeutics-presents-overview-conditionally-activated/ (2022).
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Advance in peptide-based drug development: delivery platforms, therapeutics and vaccines
Xiao, W., Jiang, W., Chen, Z., Huang, Y., Mao, J., Zheng, W., Hu, Y., & Shi, J. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-02107-5 · Cited by 449
Antibody–Drug Conjugates (ADCs): current and future biopharmaceuticals
Wang, R., Hu, B., Pan, Z., Mo, C., Zhao, X., Liu, G., Hou, P., Cui, Q., Zhao, X., Wang, W., et al. (2025) · Journal of Hematology & Oncology · doi:10.1186/s13045-025-01704-3 · Cited by 331
Xu, G., Jin, J., Fu, Z., Wang, G., Lei, X., Xu, J., & Wang, J. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02312-w · Cited by 320
Cancer therapy with antibodies
Paul, S., Konig, M. F., Pardoll, D. M., Bettegowda, C., Papadopoulos, N., Wright, K. M., Gabelli, S. B., Ho, M., van Elsas, A., & Zhou, S. (2024) · Nature reviews. Cancer · doi:10.1038/s41568-024-00690-x · Cited by 292
The Journey of Antibody–Drug Conjugates: Lessons Learned from 40 Years of Development
Colombo, R., Tarantino, P., Rich, J. R., LoRusso, P. M., & de Vries, E. G. E. (2024) · Cancer Discovery · doi:10.1158/2159-8290.cd-24-0708 · Cited by 254
Metadata
- Authors
- Tsuchikama, K., Anami, Y., Ha, S. Y. Y., & Yamazaki, C. M.
- Affiliations
- Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases (US)
- Corresponding author
- Tsuchikama, Kyoji
- Venue
- Nature Reviews Clinical Oncology
- Published
- 2024-01-08
- Volume
- 21
- Issue
- 3
- Pages
- 203-223
- ISSN
- 1759-4774 (ISSN-L)
- 1759-4782
- OpenAlex
- W4390673654
- Cited by
- 659
- References
- 248
- Citations by year
- 2026: 282 · 2025: 270 · 2024: 106
- FWCI
- 42.66
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Nature Reviews Clinical Oncology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Defense (W81XWH1910598, W81XWH)
- National Institutes of Health (W81XWH)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Monoclonal and Polyclonal Antibodies Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Degradation and Inhibitors
- Life Sciences › Immunology and Microbiology › Immunology › Toxin Mechanisms and Immunotoxins
- Keywords
- antibody-drug conjugates, drug resistance, tumor heterogeneity, linker chemistry, chemical conjugation, payload design, patient stratification, biomarkers, treatment-refractory cancer, multimodal cancer therapy
- MeSH terms
- Antibodies, Monoclonal, Antineoplastic Agents, Pharmaceutical Preparations, Humans, Neoplasms, Immunoconjugates
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