{"title":"作为实体瘤治疗药物的单域抗体","authors":"Mingkai Wang , Tianlei Ying , Yanling Wu","doi":"10.1016/j.apsb.2024.03.016","DOIUrl":null,"url":null,"abstract":"<div><p>Single-domain antibodies (sdAbs), initially identified in camelids or sharks and commonly referred to as nanobodies or VNARs, have emerged as a promising alternative to conventional therapeutic antibodies. These sdAbs have many superior physicochemical and pharmacological properties, including small size, good solubility and thermostability, easier accessible epitopes, and strong tissue penetration. However, the inherent challenges associated with the animal origin of sdAbs limit their clinical use. In recent years, various innovative humanization technologies, including complementarity-determining region (CDR) grafting or complete engineering of fully human sdAbs, have been developed to mitigate potential immunogenicity issues and enhance their compatibility. This review provides a comprehensive exploration of sdAbs, emphasizing their distinctive features and the progress in humanization methodologies. In addition, we provide an overview of the recent progress in developing drugs and therapeutic strategies based on sdAbs and their potential in solid tumor treatment, such as sdAb–drug conjugates, multispecific sdAbs, sdAb-based delivery systems, and sdAb-based cell therapy.</p></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":null,"pages":null},"PeriodicalIF":14.7000,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2211383524000984/pdfft?md5=7642d0cebe6f3d1ce84084b306b8b692&pid=1-s2.0-S2211383524000984-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Single-domain antibodies as therapeutics for solid tumor treatment\",\"authors\":\"Mingkai Wang , Tianlei Ying , Yanling Wu\",\"doi\":\"10.1016/j.apsb.2024.03.016\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Single-domain antibodies (sdAbs), initially identified in camelids or sharks and commonly referred to as nanobodies or VNARs, have emerged as a promising alternative to conventional therapeutic antibodies. These sdAbs have many superior physicochemical and pharmacological properties, including small size, good solubility and thermostability, easier accessible epitopes, and strong tissue penetration. However, the inherent challenges associated with the animal origin of sdAbs limit their clinical use. In recent years, various innovative humanization technologies, including complementarity-determining region (CDR) grafting or complete engineering of fully human sdAbs, have been developed to mitigate potential immunogenicity issues and enhance their compatibility. This review provides a comprehensive exploration of sdAbs, emphasizing their distinctive features and the progress in humanization methodologies. In addition, we provide an overview of the recent progress in developing drugs and therapeutic strategies based on sdAbs and their potential in solid tumor treatment, such as sdAb–drug conjugates, multispecific sdAbs, sdAb-based delivery systems, and sdAb-based cell therapy.</p></div>\",\"PeriodicalId\":6906,\"journal\":{\"name\":\"Acta Pharmaceutica Sinica. B\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":14.7000,\"publicationDate\":\"2024-07-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S2211383524000984/pdfft?md5=7642d0cebe6f3d1ce84084b306b8b692&pid=1-s2.0-S2211383524000984-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Acta Pharmaceutica Sinica. B\",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2211383524000984\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Acta Pharmaceutica Sinica. B","FirstCategoryId":"92","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2211383524000984","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
Single-domain antibodies as therapeutics for solid tumor treatment
Single-domain antibodies (sdAbs), initially identified in camelids or sharks and commonly referred to as nanobodies or VNARs, have emerged as a promising alternative to conventional therapeutic antibodies. These sdAbs have many superior physicochemical and pharmacological properties, including small size, good solubility and thermostability, easier accessible epitopes, and strong tissue penetration. However, the inherent challenges associated with the animal origin of sdAbs limit their clinical use. In recent years, various innovative humanization technologies, including complementarity-determining region (CDR) grafting or complete engineering of fully human sdAbs, have been developed to mitigate potential immunogenicity issues and enhance their compatibility. This review provides a comprehensive exploration of sdAbs, emphasizing their distinctive features and the progress in humanization methodologies. In addition, we provide an overview of the recent progress in developing drugs and therapeutic strategies based on sdAbs and their potential in solid tumor treatment, such as sdAb–drug conjugates, multispecific sdAbs, sdAb-based delivery systems, and sdAb-based cell therapy.
Acta Pharmaceutica Sinica. BPharmacology, Toxicology and Pharmaceutics-General Pharmacology, Toxicology and Pharmaceutics
CiteScore
22.40
自引率
5.50%
发文量
1051
审稿时长
19 weeks
期刊介绍:
The Journal of the Institute of Materia Medica, Chinese Academy of Medical Sciences, and the Chinese Pharmaceutical Association oversees the peer review process for Acta Pharmaceutica Sinica. B (APSB).
Published monthly in English, APSB is dedicated to disseminating significant original research articles, rapid communications, and high-quality reviews that highlight recent advances across various pharmaceutical sciences domains. These encompass pharmacology, pharmaceutics, medicinal chemistry, natural products, pharmacognosy, pharmaceutical analysis, and pharmacokinetics.
A part of the Acta Pharmaceutica Sinica series, established in 1953 and indexed in prominent databases like Chemical Abstracts, Index Medicus, SciFinder Scholar, Biological Abstracts, International Pharmaceutical Abstracts, Cambridge Scientific Abstracts, and Current Bibliography on Science and Technology, APSB is sponsored by the Institute of Materia Medica, Chinese Academy of Medical Sciences, and the Chinese Pharmaceutical Association. Its production and hosting are facilitated by Elsevier B.V. This collaborative effort ensures APSB's commitment to delivering valuable contributions to the pharmaceutical sciences community.