A cell-based phenotypic library selection and screening approach for the de novo discovery of novel functional chimeric antigen receptors.

Details

Ressource 1Download: 35064152_BIB_7D41964E1822.pdf (3094.92 [Ko])
State: Public
Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_7D41964E1822
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
A cell-based phenotypic library selection and screening approach for the de novo discovery of novel functional chimeric antigen receptors.
Journal
Scientific reports
Author(s)
Fierle J.K., Abram-Saliba J., Atsaves V., Brioschi M., de Tiani M., Reichenbach P., Irving M., Coukos G., Dunn S.M.
ISSN
2045-2322 (Electronic)
ISSN-L
2045-2322
Publication state
Published
Issued date
21/01/2022
Peer-reviewed
Oui
Volume
12
Number
1
Pages
1136
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
Anti-tumor therapies that seek to exploit and redirect the cytotoxic killing and effector potential of autologous or syngeneic T cells have shown extraordinary promise and efficacy in certain clinical settings. Such cells, when engineered to express synthetic chimeric antigen receptors (CARs) acquire novel targeting and activation properties which are governed and orchestrated by, typically, antibody fragments specific for a tumor antigen of interest. However, it is becoming increasingly apparent that not all antibodies are equal in this regard, with a growing appreciation that 'optimal' CAR performance requires a consideration of multiple structural and contextual parameters. Thus, antibodies raised by classical approaches and intended for other applications often perform poorly or not at all when repurposed as CARs. With this in mind, we have explored the potential of an in vitro phenotypic CAR library discovery approach that tightly associates antibody-driven bridging of tumor and effector T cells with an informative and functionally relevant CAR activation reporter signal. Critically, we demonstrate the utility of this enrichment methodology for 'real world' de novo discovery by isolating several novel anti-mesothelin CAR-active scFv candidates.
Pubmed
Open Access
Yes
Create date
31/01/2022 10:52
Last modification date
23/11/2022 7:12
Usage data