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      癌症治疗中新型抗体偶联药物的研究进展 Translated title: Research progress on novel antibody drug conjugates in cancer therapy

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          Abstract

          传统抗体偶联药物(antibody drug conjugates,ADC)通过将单克隆抗体与细胞毒性药物相结合,实现对癌细胞的精准打击,但在稳定性、靶向性、疗效及安全性等方面依然存在诸多不足。新型ADC,如双特异性、位点特异性、双有效载荷和前药型ADC,通过同时结合2个不同抗原或表位、选择更稳定的连接子、与抗体特定氨基酸位点偶联、携带不同药物有效载荷以及采用前药策略等优化方法,在保留传统ADC作用特点的基础上,显著提高药物的稳定性、靶向性、疗效和安全性,能更好地满足临床治疗的需求。新型ADC可能会在未来的癌症治疗中发挥重要的作用。探讨新型ADC在癌症治疗中的进展并分析其优势与挑战,可为开发抗癌策略提供理论支持,为药物研发提供方向。

          Translated abstract

          Traditional antibody drug conjugates (ADC) combine monoclonal antibodies with cytotoxic drugs to accurately strike cancer cells, but there are still many shortcomings in stability, targeting, efficacy, and safety. Novel ADC, such as bi-specific, site-specific, dual-payload, and pro-drug type ADC, can be optimized by simultaneously binding 2 different antigens or epitopes, selecting more stable linkers, coupling with specific amino acid sites of antibodies, carrying different drug payloads, and adopting prodrug strategies, while retaining the characteristics of traditional ADC. Significantly improving the stability, targeting, efficacy and safety of drugs can better meet the needs of clinical treatment. Novel ADC will play a more important role in cancer treatment in the future. Discussing the progress of novel ADC in cancer treatment and analyzing their advantages and challenges can provide theoretical support for the development of anti-cancer strategies and provide directions for drug research and development.

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          Strategies and challenges for the next generation of antibody–drug conjugates

          Antibody–drug conjugate (ADCs), which aim to target highly cytotoxic drugs specifically to cancer cells, are one of the fastest growing classes of anticancer therapeutics, with more than 50 such agents currently in clinical trials. This Review discusses lessons learned and emerging strategies in the development of ADCs, including aspects such as target selection, the development of warheads, the optimization of linkers and new conjugation chemistries, and provides an overview of agents that are currently in clinical trials.
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            Antibody drug conjugate: the “biological missile” for targeted cancer therapy

            Antibody–drug conjugate (ADC) is typically composed of a monoclonal antibody (mAbs) covalently attached to a cytotoxic drug via a chemical linker. It combines both the advantages of highly specific targeting ability and highly potent killing effect to achieve accurate and efficient elimination of cancer cells, which has become one of the hotspots for the research and development of anticancer drugs. Since the first ADC, Mylotarg ® (gemtuzumab ozogamicin), was approved in 2000 by the US Food and Drug Administration (FDA), there have been 14 ADCs received market approval so far worldwide. Moreover, over 100 ADC candidates have been investigated in clinical stages at present. This kind of new anti-cancer drugs, known as “biological missiles”, is leading a new era of targeted cancer therapy. Herein, we conducted a review of the history and general mechanism of action of ADCs, and then briefly discussed the molecular aspects of key components of ADCs and the mechanisms by which these key factors influence the activities of ADCs. Moreover, we also reviewed the approved ADCs and other promising candidates in phase-3 clinical trials and discuss the current challenges and future perspectives for the development of next generations, which provide insights for the research and development of novel cancer therapeutics using ADCs.
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              The expanding role of prodrugs in contemporary drug design and development

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                Author and article information

                Journal
                Zhong Nan Da Xue Xue Bao Yi Xue Ban
                Zhong Nan Da Xue Xue Bao Yi Xue Ban
                zndx
                Journal of Central South University Medical Sciences
                中南大学出版社 (湖南省长沙市湘雅路110号湘雅医学院 )
                1672-7347
                28 February 2024
                : 49
                : 2
                : 296-304
                Affiliations
                [1] [1 ] 湖南省肿瘤医院胸部内一科 长沙 410013 [1 ] Thoracic Medicine Department 1, Hunan Cancer Hospital Changsha 410013
                [2] [2 ] 湖南科技大学生命科学与健康学院 ,湖南 湘潭 411201 [2 ] College of Life Science and Health, Hunan University of Science and Technology Xiangtan Hunan 411201 China
                Author notes
                张乐蒙,Email: zhanglemeng@ 123456hnca.org.cn , ORCID: 0009-0009-7649-0652

                李雨凝,Email: 1224284589@ 123456qq.com , ORCID: 0009-0002-5738-7894

                Article
                1672-7347(2024)02-0296-09 230418
                10.11817/j.issn.1672-7347.2024.230418
                11103054
                38755726
                b8c1e260-571d-42e0-9286-df3d2cf5acfe
                ©Journal of Central South University (Medical Science). All rights reserved.

                开放获取 (Open access):本文遵循知识共享许可协议,允许第三方用户按照署名-非商业性使用-禁止演绎4.0(CC BY-NC-ND 4.0)的方式,在任何媒介以任何形式复制、传播本作品( https://creativecommons.org/licenses/by-nc-nd/4.0/)。

                History
                : 26 September 2023
                Funding
                Funded by: 湖南省自然科学基金
                Award ID: 2023JJ60039┫。This work was supported by the Natural Science Foundation of Hunan Province
                Award ID: China ┣2023JJ60039
                Categories
                Reviews

                抗体偶联药物,癌症,双特异性,位点特异性,双有效载荷,前药型,antibody drug conjugates,cancer,bi-specific,site-specific,dual payload,pro-drug type

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