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dc.contributor.authorKlampatsa, Aen_US
dc.contributor.authorLeibowitz, MSen_US
dc.contributor.authorSun, Jen_US
dc.contributor.authorLiousia, Men_US
dc.contributor.authorArguiri, Een_US
dc.contributor.authorAlbelda, SMen_US
dc.date.accessioned2020-09-30T13:45:34Z
dc.date.issued2020-09
dc.identifier.citationMolecular therapy oncolytics, 2020, 18 pp. 360 - 371
dc.identifier.issn2372-7705
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/4105
dc.identifier.eissn2372-7705
dc.identifier.doi10.1016/j.omto.2020.07.005
dc.description.abstractThe therapeutic efficacy of adoptive transfer of T cells transduced with chimeric antigen receptors (CARs) has been limited in the treatment of solid cancers, partly due to tumor antigen heterogeneity. Overcoming lack of universal tumor antigen expression would be achieved if CAR T cells could induce bystander effects. To study this process, we developed a system where CAR T cells targeting mesothelin could cure tumors containing 100% antigen-positive cells in immunocompetent mice. Using this model, we found that the CAR T cells were unable to cure tumors, even when only 10% of the tumor cells were mesothelin negative. A bystander effect was not induced by co-administration of anti-PD-1, anti-CTLA-4, or anti-TGF-β (transforming growth factor β) antibodies; agonistic CD40 antibodies; or an IDO (indoleamine 2,3-dioxygenase) inhibitor. However, pretreatment with a non-lymphodepleting dose of cyclophosphamide (CTX) prior to CAR T cells resulted in cures of tumors with up to 25% mesothelin-negative cells. The mechanism was dependent on endogenous CD8 T cells but not on basic leucine zipper transcription factor ATF-like 3 (BATF3)-dependent dendritic cells. These data suggest that CAR T cell therapy of solid tumors, in which the targeted antigen is not expressed by the vast majority of tumor cells, will not likely be successful unless combination strategies to enhance bystander effects are used.
dc.formatElectronic-eCollection
dc.format.extent360 - 371
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0
dc.titleAnalysis and Augmentation of the Immunologic Bystander Effects of CAR T Cell Therapy in a Syngeneic Mouse Cancer Model.
dc.typeJournal Article
dcterms.dateAccepted2020-07-09
rioxxterms.versionofrecord10.1016/j.omto.2020.07.005
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by-nc-nd/4.0
rioxxterms.licenseref.startdate2020-09
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfMolecular therapy oncolytics
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Thoracic Oncology Immunotherapy Group (TOIG)
pubs.publication-statusPublished
pubs.volume18
pubs.embargo.termsNot known
icr.researchteamThoracic Oncology Immunotherapy Group (TOIG)en_US
dc.contributor.icrauthorKlampatsa, Asteroen


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Except where otherwise noted, this item's license is described as https://creativecommons.org/licenses/by-nc-nd/4.0