Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/32649
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dc.contributor.authorMeyran, Deborah-
dc.contributor.authorZhu, Joe Jiang-
dc.contributor.authorButler, Jeanne-
dc.contributor.authorTantalo, Daniela-
dc.contributor.authorMacDonald, Sean-
dc.contributor.authorNguyen, Thu Ngoc-
dc.contributor.authorWang, Minyu-
dc.contributor.authorThio, Niko-
dc.contributor.authorD'Souza, Criselle-
dc.contributor.authorQin, Vicky Mengfei-
dc.contributor.authorSlaney, Clare-
dc.contributor.authorHarrison, Aaron-
dc.contributor.authorSek, Kevin-
dc.contributor.authorPetrone, Pasquale-
dc.contributor.authorThia, Kevin-
dc.contributor.authorGiuffrida, Lauren-
dc.contributor.authorScott, Andrew M-
dc.contributor.authorTerry, Rachael L-
dc.contributor.authorTran, Ben-
dc.contributor.authorDesai, Jayesh-
dc.contributor.authorPrince, H Miles-
dc.contributor.authorHarrison, Simon J-
dc.contributor.authorBeavis, Paul A-
dc.contributor.authorKershaw, Michael H-
dc.contributor.authorSolomon, Ben-
dc.contributor.authorEkert, Paul G-
dc.contributor.authorTrapani, Joseph A-
dc.contributor.authorDarcy, Phillip K-
dc.contributor.authorNeeson, Paul J-
dc.date2023-
dc.date.accessioned2023-04-14T02:47:32Z-
dc.date.available2023-04-14T02:47:32Z-
dc.date.issued2023-04-05-
dc.identifier.citationScience Translational Medicine 2023-04-05; 15(690)en_US
dc.identifier.issn1946-6242-
dc.identifier.urihttps://ahro.austin.org.au/austinjspui/handle/1/32649-
dc.description.abstractPatients who receive chimeric antigen receptor (CAR)-T cells that are enriched in memory T cells exhibit better disease control as a result of increased expansion and persistence of the CAR-T cells. Human memory T cells include stem-like CD8+ memory T cell progenitors that can become either functional stem-like T (TSTEM) cells or dysfunctional T progenitor exhausted (TPEX) cells. To that end, we demonstrated that TSTEM cells were less abundant in infused CAR-T cell products in a phase 1 clinical trial testing Lewis Y-CAR-T cells (NCT03851146), and the infused CAR-T cells displayed poor persistence in patients. To address this issue, we developed a production protocol to generate TSTEM-like CAR-T cells enriched for expression of genes in cell replication pathways. Compared with conventional CAR-T cells, TSTEM-like CAR-T cells had enhanced proliferative capacity and increased cytokine secretion after CAR stimulation, including after chronic CAR stimulation in vitro. These responses were dependent on the presence of CD4+ T cells during TSTEM-like CAR-T cell production. Adoptive transfer of TSTEM-like CAR-T cells induced better control of established tumors and resistance to tumor rechallenge in preclinical models. These more favorable outcomes were associated with increased persistence of TSTEM-like CAR-T cells and an increased memory T cell pool. Last, TSTEM-like CAR-T cells and anti-programmed cell death protein 1 (PD-1) treatment eradicated established tumors, and this was associated with increased tumor-infiltrating CD8+CAR+ T cells producing interferon-γ. In conclusion, our CAR-T cell protocol generated TSTEM-like CAR-T cells with enhanced therapeutic efficacy, resulting in increased proliferative capacity and persistence in vivo.en_US
dc.language.isoeng-
dc.titleTSTEM-like CAR-T cells exhibit improved persistence and tumor control compared with conventional CAR-T cells in preclinical models.en_US
dc.typeJournal Articleen_US
dc.identifier.journaltitleScience Translational Medicineen_US
dc.identifier.affiliationCancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne 3000, Australia.;en_US
dc.identifier.affiliationSir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne 3010, Australia.en_US
dc.identifier.affiliationUniversité de Paris, Inserm, U976 HIPI Unit, Institut de Recherche Saint-Louis, Paris F-75010, Franceen_US
dc.identifier.affiliationIntensive Careen_US
dc.identifier.affiliationSchool of Cancer Medicine, La Trobe University, Melbourne, VIC 3086, Australia.en_US
dc.identifier.affiliationOlivia Newton-John Cancer Research Instituteen_US
dc.identifier.affiliationChildren's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Sydney, NSW 1466, Australia.en_US
dc.identifier.affiliationDivision of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia.en_US
dc.identifier.affiliationCancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne 3000, Australia.;Division of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia.en_US
dc.identifier.affiliation;Kids Cancer Centre, Sydney Children's Hospital, Randwick, NSW 2031, Australiaen_US
dc.identifier.affiliationMurdoch Children's Research Institute, Royal Children's Hospital, Parkville, VIC 3052, Australia.en_US
dc.identifier.affiliationSchool of Women's and Children's Health, UNSW Sydney, Sydney, NSW 1466, Australia.en_US
dc.identifier.doi10.1126/scitranslmed.abk1900en_US
dc.type.contentTexten_US
dc.identifier.orcid0000-0003-2723-8185en_US
dc.identifier.orcid0000-0003-4416-7040en_US
dc.identifier.orcid0000-0002-5892-8990en_US
dc.identifier.orcid0000-0003-3755-3170en_US
dc.identifier.orcid0000-0002-1051-5855en_US
dc.identifier.orcid0000-0002-3089-0871en_US
dc.identifier.orcid0000-0003-2257-6388en_US
dc.identifier.orcid0000-0002-3336-1860en_US
dc.identifier.orcid0000-0002-6986-6115en_US
dc.identifier.orcid0000-0003-4634-7600en_US
dc.identifier.orcid0000-0002-4172-5628en_US
dc.identifier.orcid0000-0002-6656-295Xen_US
dc.identifier.orcid0000-0001-9124-354Xen_US
dc.identifier.orcid0000-0003-4246-9344en_US
dc.identifier.orcid0000-0002-0058-2448en_US
dc.identifier.orcid0000-0003-4555-6582en_US
dc.identifier.orcid0000-0002-2116-013Xen_US
dc.identifier.orcid0000-0002-2697-487Xen_US
dc.identifier.orcid0000-0003-3059-5730en_US
dc.identifier.orcid0000-0002-2976-8617en_US
dc.identifier.orcid0000-0003-0983-1532en_US
dc.identifier.orcid0000-0002-5303-9561en_US
dc.identifier.orcid0000-0002-2729-5887en_US
dc.identifier.pubmedid37018415-
dc.description.volume15-
dc.description.issue690-
dc.description.startpageeabk1900-
dc.subject.meshtermssecondaryImmunotherapy, Adoptive/methods-
dc.subject.meshtermssecondaryCytokines/metabolism-
dc.subject.meshtermssecondaryStem Cells/metabolism-
dc.subject.meshtermssecondaryReceptors, Antigen, T-Cell/metabolism-
local.name.researcherScott, Andrew M
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.cerifentitytypePublications-
item.fulltextNo Fulltext-
item.grantfulltextnone-
item.languageiso639-1en-
item.openairetypeJournal Article-
crisitem.author.deptMolecular Imaging and Therapy-
crisitem.author.deptOlivia Newton-John Cancer Research Institute-
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