• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

一种靶向具有富含胶原蛋白细胞外基质的肿瘤的胶原结合表皮生长因子受体抗体片段。

A collagen-binding EGFR antibody fragment targeting tumors with a collagen-rich extracellular matrix.

作者信息

Liang Hui, Li Xiaoran, Wang Bin, Chen Bing, Zhao Yannan, Sun Jie, Zhuang Yan, Shi Jiajia, Shen He, Zhang Zhijun, Dai Jianwu

机构信息

Key Laboratory for Nano-Bio Interface Research, Division of Nanobiomedicine, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123, China.

University of Chinese Academy of Sciences, Beijing 100049, China.

出版信息

Sci Rep. 2016 Feb 17;6:18205. doi: 10.1038/srep18205.

DOI:10.1038/srep18205
PMID:26883295
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4756367/
Abstract

Many tumors over-express collagen, which constitutes the physical scaffold of tumor microenvironment. Collagen has been considered to be a target for cancer therapy. The collagen-binding domain (CBD) is a short peptide, which could bind to collagen and achieve the sustained release of CBD-fused proteins in collagen scaffold. Here, a collagen-binding EGFR antibody fragment was designed and expressed for targeting the collagen-rich extracellular matrix in tumors. The antibody fragment (Fab) of cetuximab was fused with CBD (CBD-Fab) and expressed in Pichia pastoris. CBD-Fab maintained antigen binding and anti-tumor activity of cetuximab and obtained a collagen-binding ability in vitro. The results also showed CBD-Fab was mainly enriched in tumors and had longer retention time in tumors in A431 s.c. xenografts. Furthermore, CBD-Fab showed a similar therapeutic efficacy as cetuximab in A431 xenografts. Although CBD-Fab hasn't showed better therapeutic effects than cetuximab, its smaller molecular and special target may be applicable as antibody-drug conjugates (ADC) or immunotoxins.

摘要

许多肿瘤过度表达胶原蛋白，胶原蛋白构成肿瘤微环境的物理支架。胶原蛋白一直被认为是癌症治疗的一个靶点。胶原蛋白结合结构域（CBD）是一种短肽，它可以与胶原蛋白结合，并在胶原蛋白支架中实现与CBD融合蛋白的持续释放。在此，设计并表达了一种胶原蛋白结合表皮生长因子受体（EGFR）抗体片段，用于靶向肿瘤中富含胶原蛋白的细胞外基质。西妥昔单抗的抗体片段（Fab）与CBD融合（CBD-Fab），并在毕赤酵母中表达。CBD-Fab保留了西妥昔单抗的抗原结合能力和抗肿瘤活性，并在体外获得了胶原蛋白结合能力。结果还表明，在A431皮下异种移植瘤中，CBD-Fab主要富集于肿瘤中，且在肿瘤中的保留时间更长。此外，在A431异种移植瘤中，CBD-Fab显示出与西妥昔单抗相似的治疗效果。虽然CBD-Fab没有显示出比西妥昔单抗更好的治疗效果，但其较小的分子和特殊的靶点可能适用于抗体药物偶联物（ADC）或免疫毒素。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd9b/4756367/781ec498c3d7/srep18205-f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd9b/4756367/345fdb91063c/srep18205-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd9b/4756367/68da260ed54a/srep18205-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd9b/4756367/6565eb0fb3ad/srep18205-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd9b/4756367/bd68e3b0b99c/srep18205-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd9b/4756367/36d1ff86aee9/srep18205-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd9b/4756367/8e401e6564de/srep18205-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd9b/4756367/5b2b9bc7520b/srep18205-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd9b/4756367/781ec498c3d7/srep18205-f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd9b/4756367/345fdb91063c/srep18205-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd9b/4756367/68da260ed54a/srep18205-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd9b/4756367/6565eb0fb3ad/srep18205-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd9b/4756367/bd68e3b0b99c/srep18205-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd9b/4756367/36d1ff86aee9/srep18205-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd9b/4756367/8e401e6564de/srep18205-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd9b/4756367/5b2b9bc7520b/srep18205-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd9b/4756367/781ec498c3d7/srep18205-f8.jpg

相似文献

1
A collagen-binding EGFR antibody fragment targeting tumors with a collagen-rich extracellular matrix.一种靶向具有富含胶原蛋白细胞外基质的肿瘤的胶原结合表皮生长因子受体抗体片段。
Sci Rep. 2016 Feb 17;6:18205. doi: 10.1038/srep18205.
2
A collagen-binding EGFR single-chain Fv antibody fragment for the targeted cancer therapy.一种胶原结合型 EGFR 单链 Fv 抗体片段，可用于靶向癌症治疗。
J Control Release. 2015 Jul 10;209:101-9. doi: 10.1016/j.jconrel.2015.04.029. Epub 2015 Apr 24.
3
Bacterial production and structure-functional validation of a recombinant antigen-binding fragment (Fab) of an anti-cancer therapeutic antibody targeting epidermal growth factor receptor.细菌表达并结构功能验证了一种针对表皮生长因子受体的抗癌治疗性抗体的重组抗原结合片段 (Fab)。
Appl Microbiol Biotechnol. 2016 Dec;100(24):10521-10529. doi: 10.1007/s00253-016-7717-z. Epub 2016 Jul 28.
4
Combined epidermal growth factor receptor targeting with the tyrosine kinase inhibitor gefitinib (ZD1839) and the monoclonal antibody cetuximab (IMC-C225): superiority over single-agent receptor targeting.将表皮生长因子受体靶向治疗与酪氨酸激酶抑制剂吉非替尼（ZD1839）和单克隆抗体西妥昔单抗（IMC-C225）联合使用：优于单药受体靶向治疗。
Clin Cancer Res. 2004 Oct 1;10(19):6487-501. doi: 10.1158/1078-0432.CCR-04-0870.
5
A novel anti-EGFR monoclonal antibody inhibiting tumor cell growth by recognizing different epitopes from cetuximab.一种新型抗 EGFR 单克隆抗体，通过识别与西妥昔单抗不同表位来抑制肿瘤细胞生长。
J Biotechnol. 2010 Jan 1;145(1):84-91. doi: 10.1016/j.jbiotec.2009.09.023.
6
Isolation of a human anti-epidermal growth factor receptor Fab antibody, EG-19-11, with subnanomolar affinity from naïve immunoglobulin repertoires using a hierarchical antibody library system.采用分级抗体文库系统从天然免疫球蛋白库中分离出具有亚纳摩尔亲和力的人抗表皮生长因子受体 Fab 抗体 EG-19-11。
Immunol Lett. 2010 Nov 30;134(1):55-61. doi: 10.1016/j.imlet.2010.08.009. Epub 2010 Aug 24.
7
Bivalent binding by intermediate affinity of nimotuzumab: a contribution to explain antibody clinical profile.尼妥珠单抗的中等亲和力的双价结合：对解释抗体临床特征的贡献。
Cancer Biol Ther. 2011 Feb 15;11(4):373-82. doi: 10.4161/cbt.11.4.14097.
8
Structural basis for inhibition of the epidermal growth factor receptor by cetuximab.西妥昔单抗抑制表皮生长因子受体的结构基础。
Cancer Cell. 2005 Apr;7(4):301-11. doi: 10.1016/j.ccr.2005.03.003.
9
In vivo imaging of protease activity by Probody therapeutic activation.通过前体药物治疗激活对蛋白酶活性进行体内成像。
Biochimie. 2016 Mar;122:62-7. doi: 10.1016/j.biochi.2015.11.003. Epub 2015 Nov 4.
10
MicroSPECT/CT imaging of co-expressed HER2 and EGFR on subcutaneous human tumor xenografts in athymic mice using ¹¹¹In-labeled bispecific radioimmunoconjugates.微 SPECT/CT 成像在免疫缺陷小鼠皮下人源肿瘤异种移植模型中检测共表达 HER2 和 EGFR 的 ¹¹¹In 标记双特异性放射性免疫偶联物
Breast Cancer Res Treat. 2013 Apr;138(3):709-18. doi: 10.1007/s10549-013-2490-5. Epub 2013 Mar 24.

引用本文的文献

1
Targeting collagen in "armored and cold" tumors: Overcoming barriers to cancer therapy.靶向“坚硬且冷”肿瘤中的胶原蛋白：克服癌症治疗障碍
Cancer Pathog Ther. 2024 Nov 30;3(5):383-391. doi: 10.1016/j.cpt.2024.11.001. eCollection 2025 Sep.
2
Targeting collagen to optimize cancer immunotherapy.靶向胶原蛋白以优化癌症免疫疗法。
Exp Hematol Oncol. 2025 Jul 29;14(1):101. doi: 10.1186/s40164-025-00691-y.
3
Spatial Control of CAR T Cell Activation Using Tumor-Homing Polymers.使用肿瘤归巢聚合物对嵌合抗原受体（CAR）T细胞激活进行空间控制。

本文引用的文献

1
EpCAM-selective elimination of carcinoma cells by a novel MAP-based cytolytic fusion protein.一种基于新型MAP的溶细胞融合蛋白对癌细胞进行EpCAM选择性清除
Mol Cancer Ther. 2014 Sep;13(9):2194-202. doi: 10.1158/1535-7163.MCT-13-0781. Epub 2014 Jun 30.
2
The in vitro and in vivo toxicity of graphene quantum dots.石墨烯量子点的体外与体内毒性。
Biomaterials. 2014 Jun;35(19):5041-8. doi: 10.1016/j.biomaterials.2014.03.021. Epub 2014 Mar 28.
3
Microenvironmental regulation of tumor progression and metastasis.肿瘤演进和转移的微环境调控。
J Am Chem Soc. 2025 Feb 12;147(6):5149-5161. doi: 10.1021/jacs.4c15442. Epub 2025 Feb 4.
4
Collagen in hepatocellular carcinoma: A novel biomarker and therapeutic target.肝细胞癌中的胶原：一种新的生物标志物和治疗靶点。
Hepatol Commun. 2024 Jul 5;8(7). doi: 10.1097/HC9.0000000000000489. eCollection 2024 Jul 1.
5
Understanding the matrix: collagen modifications in tumors and their implications for immunotherapy.了解基质：肿瘤中的胶原蛋白修饰及其对免疫治疗的影响。
J Transl Med. 2024 Apr 24;22(1):382. doi: 10.1186/s12967-024-05199-3.
6
Understanding the in vivo Fate of Advanced Materials by Imaging.通过成像了解先进材料的体内命运。
Adv Funct Mater. 2020 Sep 10;30(37). doi: 10.1002/adfm.201910369. Epub 2020 Apr 6.
7
Validation and identification of anoikis-related lncRNA signatures for improving prognosis in clear cell renal cell carcinoma.验证和鉴定与细胞凋亡相关的 lncRNA 标志物，以改善透明细胞肾细胞癌的预后。
Aging (Albany NY). 2024 Feb 21;16(4):3915-3933. doi: 10.18632/aging.205568.
8
Extracellular matrix remodeling in the tumor immunity.肿瘤免疫中的细胞外基质重塑。
Front Immunol. 2024 Jan 25;14:1340634. doi: 10.3389/fimmu.2023.1340634. eCollection 2023.
9
Targeting collagen in tumor extracellular matrix as a novel targeted strategy in cancer immunotherapy.将肿瘤细胞外基质中的胶原蛋白作为癌症免疫治疗的一种新型靶向策略。
Front Oncol. 2023 Aug 24;13:1225483. doi: 10.3389/fonc.2023.1225483. eCollection 2023.
10
The extracellular matrix in hepatocellular carcinoma: Mechanisms and therapeutic vulnerability.肝细胞癌中的细胞外基质：机制与治疗弱点。
Cell Rep Med. 2023 Sep 19;4(9):101170. doi: 10.1016/j.xcrm.2023.101170. Epub 2023 Aug 30.
Nat Med. 2013 Nov;19(11):1423-37. doi: 10.1038/nm.3394.
4
A novel human Fab antibody for Trop2 inhibits breast cancer growth in vitro and in vivo.一种新型人源 Trop2 Fab 抗体可抑制乳腺癌的体外和体内生长。
Int J Cancer. 2014 Mar 1;134(5):1239-49. doi: 10.1002/ijc.28451. Epub 2013 Sep 19.
5
Role of collagen matrix in tumor angiogenesis and glioblastoma multiforme progression.胶原基质在肿瘤血管生成和多形性胶质母细胞瘤进展中的作用。
Am J Pathol. 2013 Oct;183(4):1293-1305. doi: 10.1016/j.ajpath.2013.06.026. Epub 2013 Aug 5.
6
Collagen VI in cancer and its biological mechanisms.胶原 VI 在癌症中的作用及其生物学机制。
Trends Mol Med. 2013 Jul;19(7):410-7. doi: 10.1016/j.molmed.2013.04.001. Epub 2013 Apr 30.
7
Acidity generated by the tumor microenvironment drives local invasion.肿瘤微环境产生的酸度会促进局部浸润。
Cancer Res. 2013 Mar 1;73(5):1524-35. doi: 10.1158/0008-5472.CAN-12-2796. Epub 2013 Jan 3.
8
Targeting the tumor microenvironment for cancer therapy.针对肿瘤微环境的癌症治疗。
Clin Chem. 2013 Jan;59(1):85-93. doi: 10.1373/clinchem.2012.185363. Epub 2012 Nov 28.
9
Cetuximab-mediated tumor regression depends on innate and adaptive immune responses.西妥昔单抗介导的肿瘤消退依赖于先天和适应性免疫反应。
Mol Ther. 2013 Jan;21(1):91-100. doi: 10.1038/mt.2012.184. Epub 2012 Sep 18.
10
Therapeutic monoclonal antibodies: strategies and challenges for biosimilars development.治疗性单克隆抗体：生物类似药开发的策略和挑战。
Curr Med Chem. 2012;19(26):4445-50. doi: 10.2174/092986712803251485.