DC Field | Value | Language |
---|---|---|
dc.contributor.author | Giordano-Attianese, Greta | ko |
dc.contributor.author | Gainza, Pablo | ko |
dc.contributor.author | Gray-Gaillard, Elise | ko |
dc.contributor.author | Cribioli, Elisabetta | ko |
dc.contributor.author | Shui, Sailan | ko |
dc.contributor.author | Kim, Seonghoon | ko |
dc.contributor.author | Kwak, Mi-Jeong | ko |
dc.contributor.author | Vollers, Sabrina | ko |
dc.contributor.author | Osorio, Angel De Jesus Corria | ko |
dc.contributor.author | Reichenbach, Patrick | ko |
dc.contributor.author | Bonet, Jaume | ko |
dc.contributor.author | Oh, Byung-Ha | ko |
dc.contributor.author | Irving, Melita | ko |
dc.contributor.author | Coukos, George | ko |
dc.contributor.author | Correia, Bruno E. | ko |
dc.date.accessioned | 2020-10-20T02:56:01Z | - |
dc.date.available | 2020-10-20T02:56:01Z | - |
dc.date.created | 2020-02-18 | - |
dc.date.created | 2020-02-18 | - |
dc.date.created | 2020-02-18 | - |
dc.date.issued | 2020-04 | - |
dc.identifier.citation | NATURE BIOTECHNOLOGY, v.38, no.4, pp.426 - 432 | - |
dc.identifier.issn | 1087-0156 | - |
dc.identifier.uri | http://hdl.handle.net/10203/276712 | - |
dc.description.abstract | The activity of CAR-T cells is reversibly halted with a small-molecule drug. Approaches to increase the activity of chimeric antigen receptor (CAR)-T cells against solid tumors may also increase the risk of toxicity and other side effects. To improve the safety of CAR-T-cell therapy, we computationally designed a chemically disruptable heterodimer (CDH) based on the binding of two human proteins. The CDH self-assembles, can be disrupted by a small-molecule drug and has a high-affinity protein interface with minimal amino acid deviation from wild-type human proteins. We incorporated the CDH into a synthetic heterodimeric CAR, called STOP-CAR, that has an antigen-recognition chain and a CD3 zeta- and CD28-containing endodomain signaling chain. We tested STOP-CAR-T cells specific for two antigens in vitro and in vivo and found similar antitumor activity compared to second-generation (2G) CAR-T cells. Timed administration of the small-molecule drug dynamically inactivated the activity of STOP-CAR-T cells. Our work highlights the potential for structure-based design to add controllable elements to synthetic cellular therapies. | - |
dc.language | English | - |
dc.publisher | NATURE PUBLISHING GROUP | - |
dc.title | A computationally designed chimeric antigen receptor provides a small-molecule safety switch for T-cell therapy | - |
dc.type | Article | - |
dc.identifier.wosid | 000510822200003 | - |
dc.identifier.scopusid | 2-s2.0-85079899789 | - |
dc.type.rims | ART | - |
dc.citation.volume | 38 | - |
dc.citation.issue | 4 | - |
dc.citation.beginningpage | 426 | - |
dc.citation.endingpage | 432 | - |
dc.citation.publicationname | NATURE BIOTECHNOLOGY | - |
dc.identifier.doi | 10.1038/s41587-019-0403-9 | - |
dc.contributor.localauthor | Oh, Byung-Ha | - |
dc.contributor.nonIdAuthor | Giordano-Attianese, Greta | - |
dc.contributor.nonIdAuthor | Gainza, Pablo | - |
dc.contributor.nonIdAuthor | Gray-Gaillard, Elise | - |
dc.contributor.nonIdAuthor | Cribioli, Elisabetta | - |
dc.contributor.nonIdAuthor | Shui, Sailan | - |
dc.contributor.nonIdAuthor | Vollers, Sabrina | - |
dc.contributor.nonIdAuthor | Osorio, Angel De Jesus Corria | - |
dc.contributor.nonIdAuthor | Reichenbach, Patrick | - |
dc.contributor.nonIdAuthor | Bonet, Jaume | - |
dc.contributor.nonIdAuthor | Irving, Melita | - |
dc.contributor.nonIdAuthor | Coukos, George | - |
dc.contributor.nonIdAuthor | Correia, Bruno E. | - |
dc.description.isOpenAccess | N | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordPlus | MEMBRANE ANTIGEN | - |
dc.subject.keywordPlus | BH3-ONLY PROTEINS | - |
dc.subject.keywordPlus | B-CELL | - |
dc.subject.keywordPlus | PROSTATE | - |
dc.subject.keywordPlus | INHIBITOR | - |
dc.subject.keywordPlus | BINDING | - |
dc.subject.keywordPlus | SYSTEM | - |
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