DC Field | Value | Language |
---|---|---|
dc.contributor.author | Lee, Young-Ho | ko |
dc.contributor.author | Lee, Hyeong Ji | ko |
dc.contributor.author | Kim, Hyung Cheol | ko |
dc.contributor.author | Lee, Yujean | ko |
dc.contributor.author | Nam, Su Kyung | ko |
dc.contributor.author | Hupperetz, Cedric | ko |
dc.contributor.author | Ma, Jennifer S. Y. | ko |
dc.contributor.author | Wang, Xinxin | ko |
dc.contributor.author | Singer, Oded | ko |
dc.contributor.author | Kim, Won Seog | ko |
dc.contributor.author | Kim, Seok Jin | ko |
dc.contributor.author | Koh, Youngil | ko |
dc.contributor.author | Jung, Inkyung | ko |
dc.contributor.author | Kim, Chan Hyuk | ko |
dc.date.accessioned | 2022-02-22T06:42:50Z | - |
dc.date.available | 2022-02-22T06:42:50Z | - |
dc.date.created | 2022-02-22 | - |
dc.date.created | 2022-02-22 | - |
dc.date.created | 2022-02-22 | - |
dc.date.issued | 2022-02 | - |
dc.identifier.citation | MOLECULAR THERAPY, v.30, no.2, pp.579 - 592 | - |
dc.identifier.issn | 1525-0016 | - |
dc.identifier.uri | http://hdl.handle.net/10203/292345 | - |
dc.description.abstract | CD19-targeting chimeric antigen receptor (CAR) T cells have become an important therapeutic option for patients with relapsed and refractory B cell malignancies. However, a significant portion of patients still do not benefit from the therapy owing to various resistance mechanisms, including high expression of multiple inhibitory immune checkpoint receptors. Here, we report a lentiviral two-in-one CAR T approach in which two checkpoint receptors are downregulated simultaneously by a dual short hairpin RNA cassette integrated into a CAR vector. Using this system, we evaluated CD19-targeting CAR T cells in the context of four different checkpoint combinationsPD-1/TIM-3, PD-1/LAG-3, PD-1/CTLA-4, and PD-1/TIGITand found that CAR T cells with PD-1/TIGIT downregulation uniquely exerted synergistic antitumor effects. Importantly, functional and phenotypic analyses suggested that downregulation of PD-1 enhances short-term effector function, whereas downregulation of TIGIT is primarily responsible for maintaining a less differentiated/exhausted state, providing a potential mechanism for the observed synergy. The PD-1/TIGIT-downregulated CAR T cells generated from diffuse large B cell lymphoma patient-derived T cells also showed robust antitumor activity and significantly improved persistence in vivo. The efficacy and safety of PD-1/TIGIT-downregulated CD19-targeting CAR T cells are currently being evaluated in adult patients with relapsed or refractory large B cell lymphoma | - |
dc.language | English | - |
dc.publisher | CELL PRESS | - |
dc.title | PD-1 and TIGIT downregulation distinctly affect the effector and early memory phenotypes of CD19-targeting CAR T cells | - |
dc.type | Article | - |
dc.identifier.wosid | 000752482600007 | - |
dc.identifier.scopusid | 2-s2.0-85117965421 | - |
dc.type.rims | ART | - |
dc.citation.volume | 30 | - |
dc.citation.issue | 2 | - |
dc.citation.beginningpage | 579 | - |
dc.citation.endingpage | 592 | - |
dc.citation.publicationname | MOLECULAR THERAPY | - |
dc.identifier.doi | 10.1016/j.ymthe.2021.10.004 | - |
dc.contributor.localauthor | Jung, Inkyung | - |
dc.contributor.localauthor | Kim, Chan Hyuk | - |
dc.contributor.nonIdAuthor | Lee, Young-Ho | - |
dc.contributor.nonIdAuthor | Lee, Hyeong Ji | - |
dc.contributor.nonIdAuthor | Kim, Hyung Cheol | - |
dc.contributor.nonIdAuthor | Lee, Yujean | - |
dc.contributor.nonIdAuthor | Nam, Su Kyung | - |
dc.contributor.nonIdAuthor | Ma, Jennifer S. Y. | - |
dc.contributor.nonIdAuthor | Wang, Xinxin | - |
dc.contributor.nonIdAuthor | Singer, Oded | - |
dc.contributor.nonIdAuthor | Kim, Won Seog | - |
dc.contributor.nonIdAuthor | Kim, Seok Jin | - |
dc.contributor.nonIdAuthor | Koh, Youngil | - |
dc.description.isOpenAccess | N | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordAuthor | CAR T | - |
dc.subject.keywordAuthor | CD19 | - |
dc.subject.keywordAuthor | clinical trial | - |
dc.subject.keywordAuthor | immune checkpoints | - |
dc.subject.keywordAuthor | PD-1 | - |
dc.subject.keywordAuthor | shRNA | - |
dc.subject.keywordAuthor | TIGIT | - |
dc.subject.keywordPlus | TERM-FOLLOW-UP | - |
dc.subject.keywordPlus | BLOCKADE | - |
dc.subject.keywordPlus | EXHAUSTION | - |
dc.subject.keywordPlus | CD8(+) | - |
dc.subject.keywordPlus | PATHWAYS | - |
dc.subject.keywordPlus | THERAPY | - |
dc.subject.keywordPlus | RESISTANCE | - |
dc.subject.keywordPlus | LEUKEMIA | - |
dc.subject.keywordPlus | EFFICACY | - |
dc.subject.keywordPlus | SUBSETS | - |
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