https://scholars.lib.ntu.edu.tw/handle/123456789/522082
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.author | CHING-YAO YANG | en_US |
dc.contributor.author | Fan M.H. | en_US |
dc.contributor.author | Miao C.H. | en_US |
dc.contributor.author | Liao Y.J. | en_US |
dc.contributor.author | RAY-HWANG YUAN | en_US |
dc.contributor.author | Liu C.L. | en_US |
dc.creator | Yang, Cy;Fan, Mh;Miao, Ch;Liao, Yj;Ray-Hwang Yuan;Liu, Cl | - |
dc.date.accessioned | 2020-11-24T02:19:49Z | - |
dc.date.available | 2020-11-24T02:19:49Z | - |
dc.date.issued | 2020 | - |
dc.identifier.issn | 2372-7705 | - |
dc.identifier.uri | https://scholars.lib.ntu.edu.tw/handle/123456789/522082 | - |
dc.description.abstract | Yang et al. developed armed third-generation PD-L1-targeted ACR/CAR T cells utilizing a PD-1/PD-L1 immune checkpoint axis. Both engineered CAR T cells significantly improved tumor control and survival in models of PD-L1-expressed pancreatic cancers. ? 2020 The Author(s)Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with a 5-year survival rate of 9%. Major obstacles to successful treatment of pancreatic cancer are the immunosuppressive tumor microenvironment (TME) and antigenic complexity or heterogeneity. Programmed death-ligand 1 (PD-L1) is expressed on PDAC and immunosuppressed cells within the TME, providing suitable immunotherapy targets. We applied a chimeric antigen receptor (CAR) strategy to target immune checkpoint programmed death-1 (PD-1)/PD-L1 interactions. Lentiviral vectors were used to express the extracellular domain of human PD-1 (PD-1-CD28-4-1BB activating chimeric receptor [PD1ACR]) or the single-chain variable fragment (scFv) region of anti-PD-L1 (PDL1CAR) that binds to PD-L1, and each was fused to intracellular signaling domains containing CD3 zeta, CD28, and 4-1BB (CD137). Both engineered CAR T cells recognized and eliminated PD-L1-overexpressing CFPAC1 cells efficiently at approximately 80% in vitro. Adoptive transfer of both CAR T cells enhanced T cell persistence and induced specific regression of established CFPAC1 cancer by >80% in both xenograft and orthotopic models. Ki67 expression in tumors decreased, whereas proinflammatory cytokines/chemokines increased in CAR T cell-treated mouse sera. PD1ACR and PDL1CAR obtained a similar therapeutic efficacy. Thus, these armed third-generation PD-L1-targeted CAR T cells confer antitumor activity and the ability to combat T cell exhaustion, providing a potentially new and innovative CAR T cell immunotherapy against pancreatic cancers. ? 2020 The Author(s) | - |
dc.publisher | CELL PRESS | en_US |
dc.relation.ispartof | MOLECULAR THERAPY-ONCOLYTICS | en_US |
dc.subject.classification | [SDGs]SDG3 | - |
dc.subject.other | CD27 antigen; CD28 antigen; CD3 antigen; chimeric antigen receptor; cytotoxic T lymphocyte antigen 4; gamma interferon; hepatitis A virus cellular receptor 2; immune checkpoint inhibitor; immunological antineoplastic agent; Ki 67 antigen; L selectin; lentivirus vector; messenger RNA; platelet derived growth factor; platelet derived growth factor AA; programmed death 1 ligand 1; programmed death 1 receptor; single chain fragment variable antibody; tumor necrosis factor; tumor necrosis factor receptor superfamily member 9; unclassified drug; adoptive transfer; animal tissue; antineoplastic activity; Article; binding affinity; comparative study; controlled study; cytokine release; cytotoxicity; enzyme linked immunosorbent assay; expression vector; flow cytometry; human; immunohistochemistry; in vitro study; intracellular signaling; mouse; MTT assay; nonhuman; overall survival; pancreas cancer; priority journal; real time reverse transcription polymerase chain reaction; survival rate; T lymphocyte activation; tumor growth; tumor weight; Western blotting | - |
dc.title | Engineering Chimeric Antigen Receptor T Cells against Immune Checkpoint Inhibitors PD-1/PD-L1 for Treating Pancreatic Cancer | en_US |
dc.type | journal article | en |
dc.identifier.doi | 10.1016/j.omto.2020.05.009 | - |
dc.identifier.isi | WOS:000544101600049 | - |
dc.relation.pages | 571 | en_US |
dc.relation.journalvolume | 17 | en_US |
dc.relation.pageend | 585 | en_US |
item.fulltext | no fulltext | - |
item.cerifentitytype | Publications | - |
item.openairetype | journal article | - |
item.openairecristype | http://purl.org/coar/resource_type/c_6501 | - |
item.grantfulltext | none | - |
crisitem.author.dept | Surgery-NTUH | - |
crisitem.author.dept | Surgery | - |
crisitem.author.dept | Surgery-NTUH | - |
crisitem.author.dept | Surgery | - |
crisitem.author.dept | NTU BioMedical Park Hospital | - |
crisitem.author.orcid | 0000-0001-6312-3719 | - |
crisitem.author.orcid | 0000-0002-2767-633X | - |
crisitem.author.parentorg | National Taiwan University Hospital | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | National Taiwan University Hospital | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | National Taiwan University Hospital Hsin-Chu Branch | - |
顯示於: | 醫學系 |
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