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

Details

Serval ID
serval:BIB_0215AF947298
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Characterization of the first fully human anti-TEM1 scFv in models of solid tumor imaging and immunotoxin-based therapy.
Journal
Cancer immunology, immunotherapy
Author(s)
Yuan X., Yang M., Chen X., Zhang X., Sukhadia S., Musolino N., Bao H., Chen T., Xu C., Wang Q., Santoro S., Ricklin D., Hu J., Lin R., Yang W., Li Z., Qin W., Zhao A.
ISSN
1432-0851 (Electronic)
ISSN-L
0340-7004
Publication state
Published
Issued date
03/2017
Peer-reviewed
Oui
Volume
66
Number
3
Pages
367-378
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
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.

Pubmed
Web of science
Create date
22/12/2016 12:49
Last modification date
20/08/2019 12:24
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