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Pooled screening of CAR T cells identifies diverse immune signaling domains for next-generation immunotherapies
DC Field | Value | Language |
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dc.contributor.author | 황병진 | - |
dc.date.accessioned | 2022-12-22T05:13:44Z | - |
dc.date.available | 2022-12-22T05:13:44Z | - |
dc.date.issued | 2022-11 | - |
dc.identifier.issn | 1946-6234 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/192336 | - |
dc.description.abstract | Chimeric antigen receptors (CARs) repurpose natural signaling components to retarget T cells to refractory cancers but have shown limited efficacy in persistent, recurrent malignancies. Here, we introduce "CAR Pooling," a multiplexed approach to rapidly identify CAR designs with clinical potential. Forty CARs with signaling domains derived from a range of immune cell lineages were evaluated in pooled assays for their ability to stimulate critical T cell effector functions during repetitive stimulation that mimics long-term tumor antigen exposure. Several domains were identified from the tumor necrosis factor (TNF) receptor family that have been primarily associated with B cells. CD40 enhanced proliferation, whereas B cell-activating factor receptor (BAFF-R) and transmembrane activator and CAML interactor (TACI) promoted cytotoxicity. These functions were enhanced relative to clinical benchmarks after prolonged antigen stimulation, and CAR T cell signaling through these domains fell into distinct states of memory, cytotoxicity, and metabolism. BAFF-R CAR T cells were enriched for a highly cytotoxic transcriptional signature previously associated with positive clinical outcomes. We also observed that replacing the 4-1BB intracellular signaling domain with the BAFF-R signaling domain in a clinically validated B cell maturation antigen (BCMA)-specific CAR resulted in enhanced activity in a xenotransplant model of multiple myeloma. Together, these results show that CAR Pooling is a general approach for rapid exploration of CAR architecture and activity to improve the efficacy of CAR T cell therapies. | - |
dc.description.statementOfResponsibility | restriction | - |
dc.language | English | - |
dc.publisher | American Association for the Advancement of Science | - |
dc.relation.isPartOf | SCIENCE TRANSLATIONAL MEDICINE | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.subject.MESH | B-Cell Maturation Antigen | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | Immunotherapy | - |
dc.subject.MESH | Immunotherapy, Adoptive / methods | - |
dc.subject.MESH | Neoplasm Recurrence, Local* / metabolism | - |
dc.subject.MESH | Receptors, Chimeric Antigen* / metabolism | - |
dc.subject.MESH | Signal Transduction | - |
dc.subject.MESH | T-Lymphocytes | - |
dc.title | Pooled screening of CAR T cells identifies diverse immune signaling domains for next-generation immunotherapies | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | BioMedical Science Institute (의생명과학부) | - |
dc.contributor.googleauthor | Daniel B Goodman | - |
dc.contributor.googleauthor | Camillia S Azimi | - |
dc.contributor.googleauthor | Kendall Kearns | - |
dc.contributor.googleauthor | Alexis Talbot | - |
dc.contributor.googleauthor | Kiavash Garakani | - |
dc.contributor.googleauthor | Julie Garcia | - |
dc.contributor.googleauthor | Nisarg Patel | - |
dc.contributor.googleauthor | Byungjin Hwang | - |
dc.contributor.googleauthor | David Lee | - |
dc.contributor.googleauthor | Emily Park | - |
dc.contributor.googleauthor | Vivasvan S Vykunta | - |
dc.contributor.googleauthor | Brian R Shy | - |
dc.contributor.googleauthor | Chun Jimmie | - |
dc.contributor.googleauthor | Justin Eyquem | - |
dc.contributor.googleauthor | Alexander Marson | - |
dc.contributor.googleauthor | Jeffrey A Bluestone | - |
dc.contributor.googleauthor | Kole T Roybal | - |
dc.identifier.doi | 10.1126/scitranslmed.abm14 | - |
dc.contributor.localId | A06348 | - |
dc.relation.journalcode | J02645 | - |
dc.identifier.eissn | 1946-6242 | - |
dc.identifier.pmid | 36350984 | - |
dc.identifier.url | https://www.science.org/doi/10.1126/scitranslmed.abm1463?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed | - |
dc.contributor.alternativeName | Hwang, Byungjin | - |
dc.contributor.affiliatedAuthor | 황병진 | - |
dc.citation.volume | 14 | - |
dc.citation.number | 670 | - |
dc.citation.startPage | eabm1463 | - |
dc.identifier.bibliographicCitation | SCIENCE TRANSLATIONAL MEDICINE, Vol.14(670) : eabm1463, 2022-11 | - |
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