Advances and perspectives of next-generation antitumor antibody-based modalities: Structural innovation and target-driven strategies.
- 1Clinical Trial Center, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
- 2Department of Clinical Medicine, The Second School of Clinical Medicine, Anhui Medical University, Hefei 230032, China.
Abstract
Antibody-based therapies have gained significant traction in oncology, as evidenced by their prominent presence at international conferences such as American Association for Cancer Research (AACR) and American Society of Clinical Oncology (ASCO). Modalities including antibody-drug conjugates (ADCs), bispecific antibodies (BsAbs), and T-cell engagers (TCEs) are increasingly recognized as pillars of precision medicine. Driven by advances in molecular engineering, antibody formats and mechanisms of action have evolved beyond conventional antigen blockade to encompass multimodal cytotoxicity and immune modulation. ADCs now leverage optimized linkers and payloads for targeted delivery and potent tumor cell killing. BsAbs simultaneously engage tumor and immune cell targets to enhance immune activation, while TCEs enable T cells to recognize intracellular antigens presented via MHC, overcoming the limitations of extracellular targeting. Emerging design strategies are increasingly tailored to target-specific features such as expression levels, internalization capacity, and cellular subtype. Innovations include non-internalizing ADCs for low-abundance targets and biased antibody architectures that preferentially activate CD8⁺ T cells. These developments are expanding the therapeutic landscape toward greater efficacy, safety, and personalization. This review outlines the global landscape of antibody drug development, highlighting a paradigm shift toward target-driven design principles that integrate structural innovation with functional precision.
Related
- Current Advances in Imaging Diagnosis of Bacterial Infectious Diseases: From Structural to Nano Imaging Modalities
- Engrailed-1 in eccrine sweat gland development and regeneration: from evolutionary innovation to therapeutic perspectives.
- Training-free generation of 4D CT and other rare acquisitions improves segmentation across modalities
- Evolution of CAR-T Therapy: Functional Engineering, Manufacturing Innovation, and Future In Vivo Strategies.
- Targeting the NLRP3 inflammasome in rheumatoid arthritis fibroblast-like synoviocytes: pathogenic mechanisms, therapeutic strategies, and translational perspectives
BibTeX
@article{sun2026advances,
title = {{Advances and perspectives of next-generation antitumor antibody-based modalities: Structural innovation and target-driven strategies.}},
author = {Liangjie Sun and Baixin Xu and Shuhang Wang and Ning Li},
journal = {Acta pharmaceutica Sinica. B},
year = {2026},
month = jun,
doi = {10.1016/j.apsb.2026.06.028},
url = {https://europepmc.org/article/MED/42948710},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Advances and perspectives of next-generation antitumor antibody-based modalities: Structural innovation and target-driven strategies.
AU - Liangjie Sun
AU - Baixin Xu
AU - Shuhang Wang
AU - Ning Li
PY - 2026
DA - 2026/06/29
JO - Acta pharmaceutica Sinica. B
DO - 10.1016/j.apsb.2026.06.028
UR - https://europepmc.org/article/MED/42948710
AB - Antibody-based therapies have gained significant traction in oncology, as evidenced by their prominent presence at international conferences such as American Association for Cancer Research (AACR) and American Society of Clinical Oncology (ASCO). Modalities including antibody-drug conjugates (ADCs), bispecific antibodies (BsAbs), and T-cell engagers (TCEs) are increasingly recognized as pillars of precision medicine. Driven by advances in molecular engineering, antibody formats and mechanisms of action have evolved beyond conventional antigen blockade to encompass multimodal cytotoxicity and immune modulation. ADCs now leverage optimized linkers and payloads for targeted delivery and potent tumor cell killing. BsAbs simultaneously engage tumor and immune cell targets to enhance immune activation, while TCEs enable T cells to recognize intracellular antigens presented via MHC, overcoming the limitations of extracellular targeting. Emerging design strategies are increasingly tailored to target-specific features such as expression levels, internalization capacity, and cellular subtype. Innovations include non-internalizing ADCs for low-abundance targets and biased antibody architectures that preferentially activate CD8⁺ T cells. These developments are expanding the therapeutic landscape toward greater efficacy, safety, and personalization. This review outlines the global landscape of antibody drug development, highlighting a paradigm shift toward target-driven design principles that integrate structural innovation with functional precision.
SN - 2211-3835
SN - 2211-3843
ER -