{"title":"抗体-药物偶联物：精确癌症治疗的当前挑战和创新解决方案。","authors":"Xingyu Zhou, Yanjie Han, Yuan Fang, Peiwen Ma, Jiawei Zhou, Yale Jiang, Shujun Xing, Qiyu Tang, Yiru Hou, Shuhang Wang, Ning Li","doi":"10.1016/j.medj.2025.100849","DOIUrl":null,"url":null,"abstract":"<p><p>Antibody-drug conjugates (ADCs) have advanced cancer therapy by combining antibody specificity with cytotoxic potency. However, clinical experience has revealed challenges limiting their efficacy and safety. This review addresses key questions in ADC development and corresponding optimization strategies. It discusses the relationship between target antigen expression and clinical response and the role of antibodies beyond targeting. Enhancing ADC distribution via bispecific targeting and probody masking is summarized. Traditional assumptions in linker design, such as favoring maximum stability, are re-evaluated to improve clinical outcomes. Innovations in linker chemistry encompass tumor microenvironment-responsive release mechanisms and bioorthogonal reactions. Emerging payload strategies like immune-stimulating ADCs (ISACs) and degrader-antibody conjugates (DACs) expand therapeutic possibilities but introduce new safety challenges. Ultimately, merely increasing ADC structural complexity is insufficient. Understanding tumor delivery barriers and bridging preclinical-clinical gaps will be vital to fully realize the potential of ADCs in precision oncology.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"100849"},"PeriodicalIF":11.8000,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Antibody-drug conjugates: Current challenges and innovative solutions for precision cancer therapy.\",\"authors\":\"Xingyu Zhou, Yanjie Han, Yuan Fang, Peiwen Ma, Jiawei Zhou, Yale Jiang, Shujun Xing, Qiyu Tang, Yiru Hou, Shuhang Wang, Ning Li\",\"doi\":\"10.1016/j.medj.2025.100849\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Antibody-drug conjugates (ADCs) have advanced cancer therapy by combining antibody specificity with cytotoxic potency. However, clinical experience has revealed challenges limiting their efficacy and safety. This review addresses key questions in ADC development and corresponding optimization strategies. It discusses the relationship between target antigen expression and clinical response and the role of antibodies beyond targeting. Enhancing ADC distribution via bispecific targeting and probody masking is summarized. Traditional assumptions in linker design, such as favoring maximum stability, are re-evaluated to improve clinical outcomes. Innovations in linker chemistry encompass tumor microenvironment-responsive release mechanisms and bioorthogonal reactions. Emerging payload strategies like immune-stimulating ADCs (ISACs) and degrader-antibody conjugates (DACs) expand therapeutic possibilities but introduce new safety challenges. Ultimately, merely increasing ADC structural complexity is insufficient. Understanding tumor delivery barriers and bridging preclinical-clinical gaps will be vital to fully realize the potential of ADCs in precision oncology.</p>\",\"PeriodicalId\":29964,\"journal\":{\"name\":\"Med\",\"volume\":\" \",\"pages\":\"100849\"},\"PeriodicalIF\":11.8000,\"publicationDate\":\"2025-09-30\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Med\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1016/j.medj.2025.100849\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Med","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1016/j.medj.2025.100849","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
Antibody-drug conjugates: Current challenges and innovative solutions for precision cancer therapy.
Antibody-drug conjugates (ADCs) have advanced cancer therapy by combining antibody specificity with cytotoxic potency. However, clinical experience has revealed challenges limiting their efficacy and safety. This review addresses key questions in ADC development and corresponding optimization strategies. It discusses the relationship between target antigen expression and clinical response and the role of antibodies beyond targeting. Enhancing ADC distribution via bispecific targeting and probody masking is summarized. Traditional assumptions in linker design, such as favoring maximum stability, are re-evaluated to improve clinical outcomes. Innovations in linker chemistry encompass tumor microenvironment-responsive release mechanisms and bioorthogonal reactions. Emerging payload strategies like immune-stimulating ADCs (ISACs) and degrader-antibody conjugates (DACs) expand therapeutic possibilities but introduce new safety challenges. Ultimately, merely increasing ADC structural complexity is insufficient. Understanding tumor delivery barriers and bridging preclinical-clinical gaps will be vital to fully realize the potential of ADCs in precision oncology.
期刊介绍：
Med is a flagship medical journal published monthly by Cell Press, the global publisher of trusted and authoritative science journals including Cell, Cancer Cell, and Cell Reports Medicine. Our mission is to advance clinical research and practice by providing a communication forum for the publication of clinical trial results, innovative observations from longitudinal cohorts, and pioneering discoveries about disease mechanisms. The journal also encourages thought-leadership discussions among biomedical researchers, physicians, and other health scientists and stakeholders. Our goal is to improve health worldwide sustainably and ethically.
Med publishes rigorously vetted original research and cutting-edge review and perspective articles on critical health issues globally and regionally. Our research section covers clinical case reports, first-in-human studies, large-scale clinical trials, population-based studies, as well as translational research work with the potential to change the course of medical research and improve clinical practice.
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