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Bispecific antibody targeting CD40 and HER2 potentiates therapeutic efficacy by reprogramming macrophages within the tumour microenvironment.

作者信息

Li Na, Li Ruonan, Ma Qiongqiong, Zhang Xiaoqi, Ma Wenxuan, Wang Yi, Duan Baoxin, Yang Kailu, Zhang Dongping, Zhang Jiashuo, Gu Manping, Wu Yaxing, Sun Jiajin, Wang Huawei, Li Anqi, Chen Fuquan, Bai Yiyang, Tian Yujie, Li Xin, Yan Yingbin, Wang Wei, Zhang Hongkai, Wang Yuan

机构信息

Institutes of Biomedical Sciences, School of Life Sciences, Inner Mongolia University, Hohhot, China.

State Key Laboratory of Medicinal Chemical Biology and College of Life Sciences, Nankai University, Tianjin, China.

出版信息

Clin Transl Med. 2025 Aug;15(8):e70428. doi: 10.1002/ctm2.70428.

DOI:10.1002/ctm2.70428
PMID:40726342
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12304727/
Abstract
摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f22/12304727/cc977dd9d53f/CTM2-15-e70428-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f22/12304727/99f09d8da1ef/CTM2-15-e70428-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f22/12304727/4f7be0182eca/CTM2-15-e70428-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f22/12304727/0d4d9b864520/CTM2-15-e70428-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f22/12304727/cc977dd9d53f/CTM2-15-e70428-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f22/12304727/99f09d8da1ef/CTM2-15-e70428-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f22/12304727/4f7be0182eca/CTM2-15-e70428-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f22/12304727/0d4d9b864520/CTM2-15-e70428-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f22/12304727/cc977dd9d53f/CTM2-15-e70428-g003.jpg

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Bispecific antibody targeting CD40 and HER2 potentiates therapeutic efficacy by reprogramming macrophages within the tumour microenvironment.靶向CD40和HER2的双特异性抗体通过重编程肿瘤微环境中的巨噬细胞增强治疗效果。
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本文引用的文献

1
The tumor-targeted CD40 agonist CEA-CD40 promotes T cell priming via a dual mode of action by increasing antigen delivery to dendritic cells and enhancing their activation.肿瘤靶向性 CD40 激动剂 CEA-CD40 通过增加抗原递呈给树突状细胞并增强其激活的双重作用模式促进 T 细胞的初始激活。
J Immunother Cancer. 2022 Mar;10(3). doi: 10.1136/jitc-2021-003264.
2
Molecular basis and therapeutic implications of CD40/CD40L immune checkpoint.CD40/CD40L 免疫检查点的分子基础和治疗意义。
Pharmacol Ther. 2021 Mar;219:107709. doi: 10.1016/j.pharmthera.2020.107709. Epub 2020 Oct 20.
3
CD40 Agonist Antibodies in Cancer Immunotherapy.
CD40 激动剂抗体在癌症免疫治疗中的应用。
Annu Rev Med. 2020 Jan 27;71:47-58. doi: 10.1146/annurev-med-062518-045435. Epub 2019 Aug 14.
4
Toxicity of an Fc-engineered anti-CD40 antibody is abrogated by intratumoral injection and results in durable antitumor immunity.Fc 工程化抗 CD40 抗体的毒性通过瘤内注射被消除，导致持久的抗肿瘤免疫。
Proc Natl Acad Sci U S A. 2018 Oct 23;115(43):11048-11053. doi: 10.1073/pnas.1810566115. Epub 2018 Oct 8.
5
Improving Efficacy and Safety of Agonistic Anti-CD40 Antibody Through Extracellular Matrix Affinity.通过细胞外基质亲和力提高激动性抗 CD40 抗体的疗效和安全性。
Mol Cancer Ther. 2018 Nov;17(11):2399-2411. doi: 10.1158/1535-7163.MCT-18-0091. Epub 2018 Aug 10.
6
Fcab-HER2 Interaction: a Ménage à Trois. Lessons from X-Ray and Solution Studies.Fcab与HER2的相互作用：三方关系。来自X射线和溶液研究的经验教训。
Structure. 2017 Jun 6;25(6):878-889.e5. doi: 10.1016/j.str.2017.04.014. Epub 2017 May 18.
7
Directed evolution of Her2/neu-binding IgG1-Fc for improved stability and resistance to aggregation by using yeast surface display.利用酵母表面展示技术对 Her2/neu 结合 IgG1-Fc 进行定向进化，以提高稳定性和抗聚集能力。
Protein Eng Des Sel. 2013 Apr;26(4):255-65. doi: 10.1093/protein/gzs102. Epub 2012 Dec 23.
8
Interaction with FcγRIIB is critical for the agonistic activity of anti-CD40 monoclonal antibody.与 FcγRIIB 的相互作用对于抗 CD40 单克隆抗体的激动活性至关重要。
J Immunol. 2011 Aug 15;187(4):1754-63. doi: 10.4049/jimmunol.1101135. Epub 2011 Jul 8.
9
Tumor imaging using a picomolar affinity HER2 binding affibody molecule.使用皮摩尔亲和力的HER2结合亲和体分子进行肿瘤成像。
Cancer Res. 2006 Apr 15;66(8):4339-48. doi: 10.1158/0008-5472.CAN-05-3521.
10
High resolution mapping of the binding site on human IgG1 for Fc gamma RI, Fc gamma RII, Fc gamma RIII, and FcRn and design of IgG1 variants with improved binding to the Fc gamma R.人IgG1上FcγRI、FcγRII、FcγRIII和FcRn结合位点的高分辨率图谱绘制以及与FcγR结合能力增强的IgG1变体设计。
J Biol Chem. 2001 Mar 2;276(9):6591-604. doi: 10.1074/jbc.M009483200. Epub 2000 Nov 28.