Soluble trivalent engagers redirect cytolytic T cell activity toward tumor endothelial marker 1.

Details

Serval ID
serval:BIB_3930B2D62A38
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Soluble trivalent engagers redirect cytolytic T cell activity toward tumor endothelial marker 1.
Journal
Cell reports. Medicine
Author(s)
Fierle J.K., Brioschi M., de Tiani M., Wetterwald L., Atsaves V., Abram-Saliba J., Petrova T.V., Coukos G., Dunn S.M.
ISSN
2666-3791 (Electronic)
ISSN-L
2666-3791
Publication state
Published
Issued date
17/08/2021
Peer-reviewed
Oui
Volume
2
Number
8
Pages
100362
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
Tumor endothelial marker 1 (TEM1) is an emerging cancer target with a unique dual expression profile. First, TEM1 is expressed in the stroma and neo-vasculature of many human carcinomas but is largely absent from healthy adult tissues. Second, TEM1 is expressed by tumor cells of mesenchymal origin, notably sarcoma. Here, we present two fully human anti-TEM1 single-chain variable fragment (scFv) reagents, namely, 1C1m and 7G22, that recognize distinct regions of the extracellular domain and possess substantially different affinities. In contrast to other, well-described anti-TEM1 binders, these fragments confer cytolytic activity when expressed as 2 <sup>nd</sup> generation chimeric antigen receptors (CARs). Moreover, both molecules selectively redirect human T cell effector functions toward TEM1 <sup>+</sup> tumor cells when incorporated into experimental soluble bispecific trivalent engagers that we term TriloBiTEs (tBs). Furthermore, systemic delivery of 1C1m-tB prevents the establishment of Ewing sarcoma tumors in a xenograft model. Our observations confirm TEM1 as a promising target for cancer immunotherapy and illustrate the prospective translational potential of certain scFv-based reagents.
Keywords
BiTE, CAR, T cell engager, TEM1, cancer immunotherapy, endosialin/CD248, sarcoma
Pubmed
Web of science
Open Access
Yes
Create date
10/09/2021 17:30
Last modification date
13/10/2021 5:43
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