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抗体药物偶联物作为癌症治疗手段的进展。

Advancements in antibody-drug conjugates as cancer therapeutics.

作者信息

Fong Jung Yin, Phuna Zhixin, Chong Di Yang, Heryanto Christophorus Manuel, Low Yu Shyan, Oh Khang Chiang, Lee Yan Huen, Ng Allan Wee Ren, In Lionel Lian Aun, Teo Michelle Yee Mun

机构信息

Department of Biotechnology, Faculty of Applied Sciences, UCSI University, Kuala Lumpur, Malaysia.

Cancer Immunotherapy Research Group (CIRG), Faculty of Applied Sciences, UCSI University, Kuala Lumpur, Malaysia.

出版信息

J Natl Cancer Cent. 2025 Apr 19;5(4):362-378. doi: 10.1016/j.jncc.2025.01.007. eCollection 2025 Aug.


DOI:10.1016/j.jncc.2025.01.007
PMID:40814440
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12346686/
Abstract

Antibody-drug conjugates (ADCs) represent a promising approach in targeted cancer therapy, combining the targeted precision of antibodies with the potency of cytotoxic payloads to selectively target tumour cell whilst minimising off-target effects. This review provides a comprehensive analysis of ADCs, encompassing their structural components, mechanisms of action, and clinical applications. It also examines recent technological advancements, particularly in antibody engineering and linker design, aimed at enhancing therapeutic efficacy and safety. The current clinical landscape is outlined, highlighting approved ADCs and promising candidates in clinical trials, while also addressing key challenges such as stability, half-life, and systemic toxicity. This review is based on an extensive literature survey from major databases such as Scopus and Web of Science, with a focus on keywords like "antibody-drug conjugates", "ADC advancements", and "next-generation ADC technologies". By integrating insights from both preclinical and clinical perspectives, we highlight the transformative potential of ADCs in advancing modern cancer therapy.

摘要

抗体药物偶联物(ADCs)是靶向癌症治疗中一种很有前景的方法,它将抗体的靶向精准性与细胞毒性药物的效力相结合,以选择性地靶向肿瘤细胞,同时将脱靶效应降至最低。本综述对ADCs进行了全面分析,涵盖其结构组成、作用机制和临床应用。它还研究了近期的技术进步,特别是在抗体工程和连接子设计方面,旨在提高治疗效果和安全性。概述了当前的临床情况,重点介绍了已获批的ADCs和临床试验中有前景的候选药物,同时也探讨了稳定性、半衰期和全身毒性等关键挑战。本综述基于对Scopus和Web of Science等主要数据库的广泛文献调查,重点关注“抗体药物偶联物”、“ADCs进展”和“下一代ADC技术”等关键词。通过整合临床前和临床观点的见解,我们强调了ADCs在推进现代癌症治疗方面的变革潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/163c/12346686/17beaa6ef81e/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/163c/12346686/512e43891a32/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/163c/12346686/474c17e41785/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/163c/12346686/0dc49508d873/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/163c/12346686/17beaa6ef81e/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/163c/12346686/512e43891a32/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/163c/12346686/474c17e41785/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/163c/12346686/0dc49508d873/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/163c/12346686/17beaa6ef81e/gr4.jpg

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Advancements in antibody-drug conjugates as cancer therapeutics.

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本文引用的文献

[1]
The combination of immune checkpoint inhibitors and antibody-drug conjugates in the treatment of urogenital tumors: a review insights from phase 2 and 3 studies.

Cell Death Dis. 2024-6-19

[2]
Bispecific antibody drug conjugates: Making 1+1>2.

Acta Pharm Sin B. 2024-5

[3]
"Negative" Impact: The Role of Payload Charge in the Physicochemical Stability of Auristatin Antibody-Drug Conjugates.

J Pharm Sci. 2024-8

[4]
Cellular senescence in cancer: molecular mechanisms and therapeutic targets.

MedComm (2020). 2024-4-24

[5]
Structure-guided engineering and molecular simulations to design a potent monoclonal antibody to target aP2 antigen for adaptive immune response instigation against type 2 diabetes.

Front Immunol. 2024

[6]
Reducing Immunogenicity by Design: Approaches to Minimize Immunogenicity of Monoclonal Antibodies.

BioDrugs. 2024-3

[7]
Engineering CD276/B7-H3-targeted antibody-drug conjugates with enhanced cancer-eradicating capability.

Cell Rep. 2023-12-26

[8]
Fc-Engineered Therapeutic Antibodies: Recent Advances and Future Directions.

Pharmaceutics. 2023-9-28

[9]
Antibody-drug conjugates in oncology: insights into Current challenges.

Expert Opin Biol Ther. 2023

[10]
Antibody-drug conjugates: Recent advances in payloads.

Acta Pharm Sin B. 2023-10

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