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Generation and proof-of-concept for allogeneic CD123 CAR-Delta One T (DOT) cells in acute myeloid leukemia

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dc.contributor.authorSánchez Martínez, Diego
dc.contributor.authorTirado, Néstor
dc.contributor.authorMensurado, Sofia
dc.contributor.authorMartínez-Moreno, Alba
dc.contributor.authorRomecín, Paola
dc.contributor.authorGutiérrez Agüera, Francisco
dc.contributor.authorCorreia, Daniel V.
dc.contributor.authorSilva-Santos, Bruno
dc.contributor.authorMenéndez, Pablo
dc.date.accessioned2024-07-25T13:22:17Z
dc.date.available2024-07-25T13:22:17Z
dc.date.issued2022
dc.description© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See http://creativecommons.org/licenses/by-nc/4.0/.pt_PT
dc.description.abstractBackground: Chimeric antigen receptor (CAR)-T cells have emerged as a breakthrough treatment for relapse/refractory hematological tumors, showing impressive complete remission rates. However, around 50% of the patients relapse before 1-year post-treatment. T-cell 'fitness' is critical to prolong CAR-T persistence and activity. Allogeneic T cells from healthy donors are less dysfunctional or exhausted than autologous patient-derived T cells; in this context, Delta One T cells (DOTs), a recently described cellular product based on MHC/HLA-independent Vδ1+γδ T cells, represent a promising allogeneic platform. Methods: Here we generated and preclinically validated, for the first time, 4-1BB-based CAR-DOTs directed against the interleukin-3α chain receptor (CD123), a target antigen widely expressed on acute myeloid leukemia (AML) blasts. Results: CD123CAR-DOTs showed vigorous, superior to control DOTs, cytotoxicity against AML cell lines and primary samples both in vitro and in vivo, even on tumor rechallenge. Conclusions: Our results provide the proof-of-concept for a DOT-based next-generation allogeneic CAR-T therapy for AML.pt_PT
dc.description.sponsorship“la Caixa” Foundation (ID 100010434) under the agreement LCF/PR/HR19/52160011 (BS-S, PM) ISCIII-RICORS within the Next Generation EU program (plan de recuperación, transformación y resilencia) (PM). CERCA/Generalitat de Catalunya (PM) Fundació Josep Carreras-Obra Social la Caixa (PM). Sara Borrell fellowship from the Instituto de Salud Carlos III (DS-M). FPU PhD Scholarship form MINECO (NT).pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationJ Immunother Cancer. 2022 Sep;10(9):e005400pt_PT
dc.identifier.doi10.1136/jitc-2022-005400pt_PT
dc.identifier.eissn2051-1426
dc.identifier.urihttp://hdl.handle.net/10451/65475
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherBMJ Publishing Group Ltd.pt_PT
dc.relation.publisherversionhttps://jitc.bmj.com/pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/pt_PT
dc.subjectAdoptive immunotherapypt_PT
dc.subjectChimeric antigen receptorspt_PT
dc.titleGeneration and proof-of-concept for allogeneic CD123 CAR-Delta One T (DOT) cells in acute myeloid leukemiapt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.issue9pt_PT
oaire.citation.titleJournal for ImmunoTherapy of Cancerpt_PT
oaire.citation.volume10pt_PT
person.familyNameMensurado Santos
person.familyNameCorreia
person.familyNameSilva-Santos
person.givenNameSofia
person.givenNameDaniel
person.givenNameBruno
person.identifierhttps://scholar.google.com/citations?user=83kKWFAAAAAJ&hl=en&oi=ao
person.identifier.ciencia-idBA10-56F0-7CAD
person.identifier.ciencia-idD51E-6517-BE6A
person.identifier.orcid0000-0002-5157-0033
person.identifier.orcid0000-0002-0784-0307
person.identifier.orcid0000-0003-4141-9302
person.identifier.scopus-author-id22952761600
person.identifier.scopus-author-id6505885924
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublicationd8b0a706-823b-47f8-9b03-6ae6b5b7e494
relation.isAuthorOfPublication03fe2016-7c70-497d-8701-8e1ce758b2a2
relation.isAuthorOfPublicationf313ff02-41ee-4014-88a1-bd641b6219bf
relation.isAuthorOfPublication.latestForDiscoveryf313ff02-41ee-4014-88a1-bd641b6219bf

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