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Characterization of the first fully human anti-TEM1 scFv in models of solid tumor imaging and immunotoxin-based therapy

Yuan, Xiaopeng and Yang, Mingjuan and Chen, Xiang and Zhang, Xuhua and Sukhadia, Shrey and Musolino, Najia and Bao, Huijing and Chen, Tingtao and Xu, Chen and Wang, Qirui and Santoro, Stephen and Ricklin, Daniel and Hu, Jia and Lin, Ruihe and Yang, Wei and Li, Zhijun and Qin, Weijun and Zhao, Aizhi. (2017) Characterization of the first fully human anti-TEM1 scFv in models of solid tumor imaging and immunotoxin-based therapy. Cancer Immunology, Immunotherapy, 66 (3). pp. 367-378.

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Official URL: http://edoc.unibas.ch/55046/

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Abstract

Tumor endothelial marker 1 (TEM1) has been identified as a novel surface marker upregulated on the blood vessels and stroma in many solid tumors. We previously isolated a novel single-chain variable fragment (scFv) 78 against TEM1 from a yeast display scFv library. Here, we evaluated the potential applications of scFv78 as a tool for tumor molecular imaging, immunotoxin-based therapy and nanotherapy. Epitope mapping, three-dimensional structure docking and affinity measurements indicated that scFv78 could bind to both human and murine TEM1, with equivalent affinity, at a well-conserved conformational epitope. The rapid internalization of scFv78 and scFv78-labeled nanoparticles was triggered after specific TEM1 binding. The scFv78-saporin immunoconjugate also exerted dose-dependent cytotoxicity with high specificity to TEM1-positive cells in vitro. Finally, specific and sensitive tumor localization of scFv78 was confirmed with optical imaging in a tumor mouse model that has highly endogenous mTEM1 expression in the vasculature. Our data indicated that scFv78, the first fully human anti-TEM1 recombinant antibody, recognizes both human and mouse TEM1 and has unique and favorable features that are advantageous for the development of imaging probes or antibody-toxin conjugates for a large spectrum of human TEM1-positive solid tumors.
Faculties and Departments:05 Faculty of Science > Departement Pharmazeutische Wissenschaften > Pharmazie > Molekulare Pharmazie (Ricklin)
UniBasel Contributors:Ricklin, Daniel
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Springer
ISSN:0340-7004
e-ISSN:1432-0851
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:20 Oct 2017 08:00
Deposited On:20 Oct 2017 08:00

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