双/多特异性抗体药物差异化研发策略
作者:
基金项目:

山东省实验室项目(SYS202205)


Differential discovery strategies of bispecific and multi-specific antibody drugs
Author:
  • 摘要
  • | |
  • 访问统计
  • |
  • 参考文献 [26]
  • |
  • 相似文献
  • |
  • 引证文献
  • | |
  • 文章评论
    摘要:

    双特异性抗体药物相比于治疗性单克隆抗体药物有效性和安全性更强,逐渐成为新一代的治疗手段。随着基因工程技术的发展和产业的成熟,双/多特异性抗体药物研究数量不断增加,应用范围也在不断拓展,为满足临床需求和创造临床价值奠定了基础。本文综述了双/多特异性抗体药物的研发阶段和适应症、靶点组合、结构形式和作用机制,并探讨了双/多特异性抗体药物研发的关键点和差异化研发策略,有助于创新药物的快速发展,为推动这一类药物的临床转化应用提供了理论支持,并为临床实践提供了更精准和有效的治疗选择。

    Abstract:

    Bispecific antibody drugs have enhanced efficacy and safety compared with therapeutic monoclonal antibody drugs, gradually becoming a new generation of effective therapies. With the development of genetic engineering and the maturity of the industry, increasing studies have been carried out on bispecific and multi-specific antibody drugs, and the application indications of these drugs are expanding, which lays a foundation for satisfying the clinical needs and creating clinical values. This paper provides a comprehensive review of the development stages, indications, target combinations, structural formats, and mechanisms of bispecific and multi-specific antibody drugs. It also discusses key points and strategies for differentiated drug discovery, facilitating the rapid development of innovative therapies, providing theoretical support for the clinical translation of these drugs, and offering more precise and effective treatment options for clinical practice.

    参考文献
    [1] BLANCO B, DOMÍNGUEZ-ALONSO C, ALVAREZ-VALLINA L. Bispecific immunomodulatory antibodies for cancer immunotherapy[J]. Clinical Cancer Research: an Official Journal of the American Association for Cancer Research, 2021, 27(20): 5457-5464.
    [2] YAO Y, HU YY, WANG F. Trispecific antibodies for cancer immunotherapy[J]. Immunology, 2023, 169(4): 389-399.
    [3] Bispecific antibodies market size, share & trends analysis report[EB/OL]. [2024-05-16]. https://straitsresearch. com/report/bispecific-antibodies-market.
    [4] van de DONK NWCJ, ZWEEGMAN S. T-cell-engaging bispecific antibodies in cancer[J]. Lancet, 2023, 402(10396): 142-158.
    [5] ZHANG TC, LIN YP, GAO Q. Bispecific antibodies targeting immunomodulatory checkpoints for cancer therapy[J]. Cancer Biology & Medicine, 2023, 20(3): 181-195.
    [6] TAPIA-GALISTEO A, ÁLVAREZ-VALLINA L, SANZ L. Bi- and trispecific immune cell engagers for immunotherapy of hematological malignancies[J]. Journal of Hematology & Oncology, 2023, 16(1): 83.
    [7] TAPIA-GALISTEO A, COMPTE M, ÁLVAREZ- VALLINA L, SANZ L. When three is not a crowd: trispecific antibodies for enhanced cancer immunotherapy[J]. Theranostics, 2023, 13(3): 1028-1041.
    [8] MARUANI A. Bispecifics and antibody-drug conjugates: A positive synergy[J]. Drug Discovery Today: Technologies, 2018, 30: 55-61.
    [9] SEGUES A, HUANG S, SIJTS A, BERRAONDO P, ZAISS DM. Opportunities and challenges of bi-specific antibodies[J]. International review of cell and molecular biology, 2022, 369: 45-70.
    [10] HOSSEINI SS, KHALILI S, BARADARAN B, BIDAR N, SHAHBAZI MA, MOSAFER J, HASHEMZAEI M, MOKHTARZADEH A, HAMBLIN MR. Bispecific monoclonal antibodies for targeted immunotherapy of solid tumors: recent advances and clinical trials[J]. International journal of biological macromolecules, 2021, 167: 1030-1047.
    [11] LABRIJN AF, RISPENS T, MEESTERS J, ROSE RJ, den BLEKER TH, LOVERIX S, van den BREMER ETJ, NEIJSSEN J, VINK T, LASTERS I, AALBERSE RC, HECK AJR, van de WINKEL JGJ, SCHUURMAN J, PARREN PWHI. Species-specific determinants in the IgG CH3 domain enable Fab-arm exchange by affecting the noncovalent CH3-CH3 interaction strength[J]. Journal of Immunology, 2011, 187(6): 3238-3246.
    [12] LABRIJN AF, MEESTERS JI, de GOEIJ BECG, van den BREMER ETJ, NEIJSSEN J, van KAMPEN MD, STRUMANE K, VERPLOEGEN S, KUNDU A, GRAMER MJ, van BERKEL PHC, van de WINKEL JGJ, SCHUURMAN J, PARREN PWHI. Efficient generation of stable bispecific IgG1 by controlled Fab-arm exchange[J]. Proceedings of the National Academy of Sciences of the United States of America, 2013, 110(13): 5145-5150.
    [13] LABRIJN AF, MEESTERS JI, PRIEM P, de JONG RN, van den BREMER ETJ, van KAMPEN MD, GERRITSEN AF, SCHUURMAN J, PARREN PWHI. Controlled Fab-arm exchange for the generation of stable bispecific IgG1[J]. Nature Protocols, 2014, 9: 2450-2463.
    [14] 李栋. 治疗性抗体药物差异化研发策略[J]. 生物工程学报, 2020, 36(11): 2327-2333. LI D. Differential discovery strategies of therapeutic antibody drugs[J]. Chinese Journal of Biotechnology, 2020, 36(11): 2327-2333(in Chinese).
    [15] LABRIJN AF, JANMAAT ML, REICHERT JM, PARREN PWHI. Bispecific antibodies: a mechanistic review of the pipeline[J]. Nature Reviews Drug Discovery, 2019, 18: 585-608.
    [16] ZHANG J, YI JZ, ZHOU PF. Development of bispecific antibodies in China: overview and prospects[J]. Antibody Therapeutics, 2020, 3(2): 126-145.
    [17] SUN YZ, YU XM, WANG X, YUAN K, WANG GF, HU LR, ZHANG GY, PEI WL, WANG LP, SUN CL, YANG P. Bispecific antibodies in cancer therapy: target selection and regulatory requirements[J]. Acta Pharmaceutica Sinica B, 2023, 13(9): 3583-3597.
    [18] WEI J, YANG YY, WANG G, LIU M. Current landscape and future directions of bispecific antibodies in cancer immunotherapy[J]. Frontiers in Immunology, 2022, 13: 1035276.
    [19] GAO XY, XU N, LI ZY, SHEN L, JI K, ZHENG Z, LIU D, LOU HM, BAI L, LIU TS, LI YX, LI YZ, FAN QX, FENG M, ZHONG HJ, HUANG Y, LOU G, WANG J, LIN XY, CHEN Y, et al. Safety and antitumour activity of cadonilimab, an anti-PD-1/CTLA-4 bispecific antibody, for patients with advanced solid tumours (COMPASSION-03): a multicentre, open-label, phase 1b/2 trial[J]. The Lancet Oncology, 2023, 24(10): 1134-1146.
    [20] ZHOU CC, TANG KJ, CHO BC, LIU BG, PAZ-ARES L, CHENG S, KITAZONO S, THIAGARAJAN M, GOLDMAN JW, SABARI JK, SANBORN RE, MANSFIELD AS, HUNG JY, BOYER M, POPAT S, MOURÃO DIAS J, FELIP E, MAJEM M, GUMUS M, KIM SW, ONO A, XIE J, BHATTACHARYA A, AGRAWAL T, SHREEVE SM, KNOBLAUCH RE, PARK K, GIRARD N. Amivantamab plus Chemotherapy in NSCLC with EGFR Ex牯慮瀠攲田琠楉据獳???ど?の???????????????扮牤?孊??嵲?婡??乯??婍????啩佮???′??伳??堳???唲′?吺?′娰??中?‰夵?????夾塛??婝?乍??????娠??丠?????婉??伬??奁???湅琠楋挬愠湋捕敍牁?扁楉猠灉攬挠楁晓楁捎?愠湒琮椠扉潮摣祯?剰?慲浡灴???愠摯癦愠湡挠敲獥??慡?獥瑤甠摰祯?晹潰捥異獴楩湤来?潳湥?牵敥獮散慥爠捩桮?瑴牨敥湲摡?睥潵牴汩摣眠楡摮整?慢湯摤?楥湳??桳椠湡愠孵?嵩???潳畡牬渠慭污?潫晩??攠浰慲瑯潣汥潤杵祲??愠浡瀠??佳湥挠潳汴潵杤祹?????ㄠ????????????? bispecific antibodies[J]. New Biotechnology, 2023, 77: 80-89.
    [22] RADHAKRISHNAN VS, DAVIES AJ. Bispecific antibodies in indolent B-cell lymphomas[J]. Frontiers in Immunology, 2024, 14: 1295599.
    [23] WU L, SEUNG E, XU L, RAO E, LORD DM, WEI RR, CORTEZ-RETAMOZO V, OSPINA B, POSTERNAK V, ULINSKI G, PIEPENHAGEN P, FRANCESCONI E, EL-MURR N, BEIL C, KIRBY P, LI AQ, FRETLAND J, VICENTE R, DENG GJ, DABDOUBI T, et al. Trispecific antibodies enhance the therapeutic efficacy of tumor-directed T cells through T cell receptor co-stimulation[J]. Nature Cancer, 2020, 1: 86-98.
    [24] WEISSER NE, SANCHES M, ESCOBAR-CABRERA E, O’TOOLE J, WHALEN E, CHAN PWY, WICKMAN G, ABRAHAM L, CHOI K, HARBOURNE B, SAMIOTAKIS A, ROJAS AH, VOLKERS G, WONG J, ATKINSON CE, BAARDSNES J, WORRALL LJ, BROWMAN D, SMITH EE, BAICHOO P, et al. An anti-HER2 biparatopic antibody that induces unique HER2 clustering and complement-dependent cytotoxicity[J]. Nature Communications, 2023, 14: 1394.
    [25] DICKOPF S, GEORGES GJ, BRINKMANN U. Format and geometries matter: structure-based design defines the functionality of bispecific antibodies[J]. Computational and Structural Biotechnology Journal, 2020, 18: 1221-1227.
    [26] HABER L, OLSON K, KELLY MP, CRAWFORD A, DiLILLO DJ, TAVARÉ R, ULLMAN E, MAO S, CANOVA L, SINESHCHEKOVA O, FINNEY J, PAWASHE A, PATEL S, MCKAY R, RIZVI S, DAMKO E, CHIU D, VAZZANA K, RAM P, MOHRS K, et al. Generation of T-cell-redirecting bispecific antibodies with differentiated profiles of cytokine release and biodistribution by CD3 affinity tuning[J]. Scientific Reports, 2021, 11: 14397.
    [27] NIE SW, WANG ZZ, MOSCOSO-CASTRO M, D’SOUZA P, LEI C, XU JQ, GU JJ. Biology drives the discovery of bispecific antibodies as innovative therapeutics[J]. Antibody The
    相似文献
    引证文献
    网友评论
    网友评论
    分享到微博
    发 布
引用本文

李栋. 双/多特异性抗体药物差异化研发策略[J]. 生物工程学报, 2024, 40(11): 3974-3984

复制
分享
文章指标
  • 点击次数:181
  • 下载次数: 268
  • HTML阅读次数: 235
  • 引用次数: 0
历史
  • 收稿日期:2024-03-07
  • 在线发布日期: 2024-11-07
  • 出版日期: 2024-11-25
文章二维码
您是第6009874位访问者
生物工程学报 ® 2025 版权所有

通信地址:中国科学院微生物研究所    邮编:100101

电话:010-64807509   E-mail:cjb@im.ac.cn

技术支持:北京勤云科技发展有限公司