Autor: |
Minutolo NG, Sharma P, Poussin M, Shaw LC, Brown DP, Hollander EE, Smole A, Rodriguez-Garcia A, Hui JZ, Zappala F, Tsourkas A, Powell DJ Jr |
Jazyk: |
angličtina |
Zdroj: |
Journal of the American Chemical Society [J Am Chem Soc] 2020 Apr 08; Vol. 142 (14), pp. 6554-6568. Date of Electronic Publication: 2020 Mar 30. |
DOI: |
10.1021/jacs.9b11622 |
Abstrakt: |
Universal immune receptors represent a rapidly emerging form of adoptive T-cell therapy with the potential to overcome safety and antigen escape challenges faced by conventional chimeric antigen receptor (CAR) T-cell therapy. By decoupling antigen recognition and T-cell signaling domains via bifunctional antigen-specific targeting ligands, universal immune receptors can regulate T-cell effector function and target multiple antigens with a single receptor. Here, we describe the development of the SpyCatcher immune receptor, the first universal immune receptor that allows for the post-translational covalent attachment of targeting ligands at the T-cell surface through the application of SpyCatcher-SpyTag chemistry. The SpyCatcher immune receptor redirected primary human T cells against a variety of tumor antigens via the addition of SpyTag-labeled targeting ligands, both in vitro and in vivo. SpyCatcher T-cell activity relied upon the presence of both target antigen and SpyTag-labeled targeting ligand, allowing for dose-dependent control of function. The mutational disruption of covalent bond formation between the receptor and the targeting ligand still permitted redirected T-cell function but significantly compromised antitumor function. Thus, the SpyCatcher immune receptor allows for rapid antigen-specific receptor assembly, multiantigen targeting, and controllable T-cell activity. |
Databáze: |
MEDLINE |
Externí odkaz: |
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