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Review

Advancements in Dual-Load Antibody–Drug Conjugates and Challenges with Quality Analysis

by
Xiaojuan Yu
1,†,
Xiao Ke
2,†,
Yao Tang
3,
Tao Tang
3,
Yongbo Ni
1,
Luyun Guo
1,
Yongfei Cui
1,
Yuting Mei
1,
Gangling Xu
1,
Gang Wu
1,
Yalan Yang
1,
Maoqin Duan
1,
Jialiang Du
1,
Meng Li
1,
Jiao Tang
2,
Shijun Yin
2,
Jiali Zuo
2,
Yanhua Xu
2,
Yonghao Zhao
2,
Yan Li
3,* and
Chuanfei Yu
1,*
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1
National Institutes for Food and Drug Control, NHC Key Laboratory of Research on Quality and Standardization of Biotech Products, NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, State Key Laboratory of Drug Regulatory Science, Beijing 102629, China
2
Chengdu Kanghong Pharmaceutical Group Co., Ltd., Chengdu 610037, China
3
Sichuan Institute for Drug Control, NMPA Center for Innovation and Research in Regulatory Science, Chengdu 611731, China
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Pharmaceuticals 2026, 19(6), 860; https://doi.org/10.3390/ph19060860 (registering DOI)
Submission received: 25 April 2026 / Revised: 15 May 2026 / Accepted: 26 May 2026 / Published: 29 May 2026
(This article belongs to the Section Biopharmaceuticals)

Abstract

Antibody–drug conjugates (ADCs) are a pivotal technology for precision cancer therapy, harnessing the synergistic effects of antibody targeting and toxin delivery. However, traditional ADCs encounter limitations in efficacy that stem from tumor resistance, heterogeneity, and intense target competition. Dual-payload ADCs (DP-ADCs) represent a promising solution to these challenges, as they leverage dual mechanisms of action that mitigate acquired drug resistance and enhance adaptability to tumor heterogeneity. The complex structure of DP-ADCs presents substantial quality control hurdles. In this manuscript, we review the current payload selection and conjugation strategies of DP-ADCs and examine recent advances in quality control research. Specifically, we analyze the analytical challenges related to the quantification of free toxins, the determination of the total antibody content, and the characterization of the drug-to-antibody ratio and its distribution. Ultimately, the aim of this work is to provide valuable guidance for future DP-ADC quality control analyses to facilitate their clinical translation and application.
Keywords: dual-payload antibody–drug conjugates; quality control; liquid chromatography–mass spectrometry; drug-to-antibody ratio; analytical methods dual-payload antibody–drug conjugates; quality control; liquid chromatography–mass spectrometry; drug-to-antibody ratio; analytical methods
Graphical Abstract

Share and Cite

MDPI and ACS Style

Yu, X.; Ke, X.; Tang, Y.; Tang, T.; Ni, Y.; Guo, L.; Cui, Y.; Mei, Y.; Xu, G.; Wu, G.; et al. Advancements in Dual-Load Antibody–Drug Conjugates and Challenges with Quality Analysis. Pharmaceuticals 2026, 19, 860. https://doi.org/10.3390/ph19060860

AMA Style

Yu X, Ke X, Tang Y, Tang T, Ni Y, Guo L, Cui Y, Mei Y, Xu G, Wu G, et al. Advancements in Dual-Load Antibody–Drug Conjugates and Challenges with Quality Analysis. Pharmaceuticals. 2026; 19(6):860. https://doi.org/10.3390/ph19060860

Chicago/Turabian Style

Yu, Xiaojuan, Xiao Ke, Yao Tang, Tao Tang, Yongbo Ni, Luyun Guo, Yongfei Cui, Yuting Mei, Gangling Xu, Gang Wu, and et al. 2026. "Advancements in Dual-Load Antibody–Drug Conjugates and Challenges with Quality Analysis" Pharmaceuticals 19, no. 6: 860. https://doi.org/10.3390/ph19060860

APA Style

Yu, X., Ke, X., Tang, Y., Tang, T., Ni, Y., Guo, L., Cui, Y., Mei, Y., Xu, G., Wu, G., Yang, Y., Duan, M., Du, J., Li, M., Tang, J., Yin, S., Zuo, J., Xu, Y., Zhao, Y., ... Yu, C. (2026). Advancements in Dual-Load Antibody–Drug Conjugates and Challenges with Quality Analysis. Pharmaceuticals, 19(6), 860. https://doi.org/10.3390/ph19060860

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