Severe hematotoxicity after CD19 CAR-T therapy is associated with suppressive immune dysregulation and limited CAR-T expansion

Hematotoxicity; Suppressive immune dysregulation

Detalles Bibliográficos
Autores: Perez, Ariel, Blumenberg , Viktoria, Bücklein, Veit, Völkl, Simon, Rejeski, Kai, Barba, Pere, IACOBONI, GLORIA
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Institución:Departament de Salut de la Generalitat de Catalunya (DS)
Repositorio:Scientia. Dipòsit d'Informació Digital del Departament de Salut
OAI Identifier:oai:scientiasalut.gencat.cat:11351/10382
Acceso en línea:https://hdl.handle.net/11351/10382
Access Level:acceso abierto
Palabra clave:Càncer
Immunoteràpia
Cèl·lules T
Antígens CD
ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Biological Therapy::Immunomodulation::Immunotherapy::Immunization::Immunization, Passive::Adoptive Transfer::Immunotherapy, Adoptive
Other subheadings::Other subheadings::Other subheadings::/adverse effects
DISEASES::Neoplasms
TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::terapia biológica::inmunomodulación::inmunoterapia::inmunización::inmunización pasiva::transferencia adoptiva::inmunoterapia adoptiva
Otros calificadores::Otros calificadores::Otros calificadores::/efectos adversos
ENFERMEDADES::neoplasias
id ES_40d4dbad64b6fd6912c5cd30cdfdff3a
oai_identifier_str oai:scientiasalut.gencat.cat:11351/10382
network_acronym_str ES
network_name_str España
repository_id_str
dc.title.none.fl_str_mv Severe hematotoxicity after CD19 CAR-T therapy is associated with suppressive immune dysregulation and limited CAR-T expansion
title Severe hematotoxicity after CD19 CAR-T therapy is associated with suppressive immune dysregulation and limited CAR-T expansion
spellingShingle Severe hematotoxicity after CD19 CAR-T therapy is associated with suppressive immune dysregulation and limited CAR-T expansion
Perez, Ariel
Càncer
Immunoteràpia
Cèl·lules T
Antígens CD
ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Biological Therapy::Immunomodulation::Immunotherapy::Immunization::Immunization, Passive::Adoptive Transfer::Immunotherapy, Adoptive
Other subheadings::Other subheadings::Other subheadings::/adverse effects
DISEASES::Neoplasms
TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::terapia biológica::inmunomodulación::inmunoterapia::inmunización::inmunización pasiva::transferencia adoptiva::inmunoterapia adoptiva
Otros calificadores::Otros calificadores::Otros calificadores::/efectos adversos
ENFERMEDADES::neoplasias
title_short Severe hematotoxicity after CD19 CAR-T therapy is associated with suppressive immune dysregulation and limited CAR-T expansion
title_full Severe hematotoxicity after CD19 CAR-T therapy is associated with suppressive immune dysregulation and limited CAR-T expansion
title_fullStr Severe hematotoxicity after CD19 CAR-T therapy is associated with suppressive immune dysregulation and limited CAR-T expansion
title_full_unstemmed Severe hematotoxicity after CD19 CAR-T therapy is associated with suppressive immune dysregulation and limited CAR-T expansion
title_sort Severe hematotoxicity after CD19 CAR-T therapy is associated with suppressive immune dysregulation and limited CAR-T expansion
dc.creator.none.fl_str_mv Perez, Ariel
Blumenberg , Viktoria
Bücklein, Veit
Völkl, Simon
Rejeski, Kai
Barba, Pere
IACOBONI, GLORIA
author Perez, Ariel
author_facet Perez, Ariel
Blumenberg , Viktoria
Bücklein, Veit
Völkl, Simon
Rejeski, Kai
Barba, Pere
IACOBONI, GLORIA
author_role author
author2 Blumenberg , Viktoria
Bücklein, Veit
Völkl, Simon
Rejeski, Kai
Barba, Pere
IACOBONI, GLORIA
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Institut Català de la Salut
[Rejeski K, Blumenberg V, Bücklein VL] Department of Medicine III – Hematology/Oncology, University Hospital, LMU Munich, Munich, Germany. Laboratory for Translational Cancer Immunology, LMU Gene Center, Munich, Germany. German Cancer Consortium (DKTK), Munich and Berlin sites, and German Cancer Research Center, Heidelberg, Germany. Bavarian Cancer Research Center (BZKF), partner sites, Munich and Erlangen, Germany. [Perez A] Department of Blood and Marrow Transplant and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, FL, USA. Blood and Marrow Transplant Program, Miami Cancer Institute, Miami, FL, USA. [Iacoboni G, Barba P] Servei d’Hematologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Servei d’Hematologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Völkl S] Bavarian Cancer Research Center (BZKF), partner sites, Munich and Erlangen, Germany. Department of Internal Medicine 5, Hematology and Oncology, Friedrich-Alexander-Universität Erlangen-Nürnberg and University Hospital Erlangen, Erlangen, Germany
Vall d'Hebron Barcelona Hospital Campus
dc.subject.none.fl_str_mv Càncer
Immunoteràpia
Cèl·lules T
Antígens CD
ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Biological Therapy::Immunomodulation::Immunotherapy::Immunization::Immunization, Passive::Adoptive Transfer::Immunotherapy, Adoptive
Other subheadings::Other subheadings::Other subheadings::/adverse effects
DISEASES::Neoplasms
TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::terapia biológica::inmunomodulación::inmunoterapia::inmunización::inmunización pasiva::transferencia adoptiva::inmunoterapia adoptiva
Otros calificadores::Otros calificadores::Otros calificadores::/efectos adversos
ENFERMEDADES::neoplasias
topic Càncer
Immunoteràpia
Cèl·lules T
Antígens CD
ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Biological Therapy::Immunomodulation::Immunotherapy::Immunization::Immunization, Passive::Adoptive Transfer::Immunotherapy, Adoptive
Other subheadings::Other subheadings::Other subheadings::/adverse effects
DISEASES::Neoplasms
TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::terapia biológica::inmunomodulación::inmunoterapia::inmunización::inmunización pasiva::transferencia adoptiva::inmunoterapia adoptiva
Otros calificadores::Otros calificadores::Otros calificadores::/efectos adversos
ENFERMEDADES::neoplasias
description Hematotoxicity; Suppressive immune dysregulation
publishDate 2023
dc.date.none.fl_str_mv 2023
2023
2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/11351/10382
url https://hdl.handle.net/11351/10382
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Science Advances;9(38)
https://doi.org/10.1126/sciadv.adg3919
dc.rights.none.fl_str_mv Attribution-NonCommercial 4.0 International
http://creativecommons.org/licenses/by-nc/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Attribution-NonCommercial 4.0 International
http://creativecommons.org/licenses/by-nc/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Association for the Advancement of Science
publisher.none.fl_str_mv American Association for the Advancement of Science
dc.source.none.fl_str_mv Scientia
reponame:Scientia. Dipòsit d'Informació Digital del Departament de Salut
instname:Departament de Salut de la Generalitat de Catalunya (DS)
instname_str Departament de Salut de la Generalitat de Catalunya (DS)
reponame_str Scientia. Dipòsit d'Informació Digital del Departament de Salut
collection Scientia. Dipòsit d'Informació Digital del Departament de Salut
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869406783788810240
spelling Severe hematotoxicity after CD19 CAR-T therapy is associated with suppressive immune dysregulation and limited CAR-T expansionPerez, ArielBlumenberg , ViktoriaBücklein, VeitVölkl, SimonRejeski, KaiBarba, PereIACOBONI, GLORIACàncerImmunoteràpiaCèl·lules TAntígens CDANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Biological Therapy::Immunomodulation::Immunotherapy::Immunization::Immunization, Passive::Adoptive Transfer::Immunotherapy, AdoptiveOther subheadings::Other subheadings::Other subheadings::/adverse effectsDISEASES::NeoplasmsTÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::terapia biológica::inmunomodulación::inmunoterapia::inmunización::inmunización pasiva::transferencia adoptiva::inmunoterapia adoptivaOtros calificadores::Otros calificadores::Otros calificadores::/efectos adversosENFERMEDADES::neoplasiasHematotoxicity; Suppressive immune dysregulationHematotoxicidad; Desregulación inmunesupresoraHematotoxicitat; Desregulació immunesupressoraProlonged cytopenias after chimeric antigen receptor (CAR) T cell therapy are a significant clinical problem and the underlying pathophysiology remains poorly understood. Here, we investigated how (CAR) T cell expansion dynamics and serum proteomics affect neutrophil recovery phenotypes after CD19-directed CAR T cell therapy. Survival favored patients with “intermittent” neutrophil recovery (e.g., recurrent neutrophil dips) compared to either “quick” or “aplastic” recovery. While intermittent patients displayed increased CAR T cell expansion, aplastic patients exhibited an unfavorable relationship between expansion and tumor burden. Proteomics of patient serum collected at baseline and in the first month after CAR-T therapy revealed higher markers of endothelial dysfunction, inflammatory cytokines, macrophage activation, and T cell suppression in the aplastic phenotype group. Prolonged neutrophil aplasia thus occurs in patients with systemic immune dysregulation at baseline with subsequently impaired CAR-T expansion and myeloid-related inflammatory changes. The association between neutrophil recovery and survival outcomes highlights critical interactions between host hematopoiesis and the immune state stimulated by CAR-T infusion.K.Rej. received a fellowship from the School of Oncology of the German Cancer Consortium (DKTK) and was funded by the Else Kröner Forschungskolleg (EKFK) within the Munich Clinician Scientist Program (MCSP). This work was supported by a grant within the Gilead Research Scholar Program (to K.Rej. and M.S.), the Bruno & Helene Jöster Foundation (to K.R., M.S.), and by a Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) research grant provided within the Sonderforschungbereich SFB-TRR 338/1 2021 – 452881907 and DFG research grant 451580403 (to M.S.). The work was further supported by the Bavarian Elite Graduate Training Network (to M.S.), the Wilhelm-Sander Stiftung (to M.S., project no. 2018.087.1), the Else-Kröner-Fresenius Stiftung (to M.S.), and the Bavarian Cancer Research Center (BZKF).American Association for the Advancement of ScienceInstitut Català de la Salut[Rejeski K, Blumenberg V, Bücklein VL] Department of Medicine III – Hematology/Oncology, University Hospital, LMU Munich, Munich, Germany. Laboratory for Translational Cancer Immunology, LMU Gene Center, Munich, Germany. German Cancer Consortium (DKTK), Munich and Berlin sites, and German Cancer Research Center, Heidelberg, Germany. Bavarian Cancer Research Center (BZKF), partner sites, Munich and Erlangen, Germany. [Perez A] Department of Blood and Marrow Transplant and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, FL, USA. Blood and Marrow Transplant Program, Miami Cancer Institute, Miami, FL, USA. [Iacoboni G, Barba P] Servei d’Hematologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Servei d’Hematologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Völkl S] Bavarian Cancer Research Center (BZKF), partner sites, Munich and Erlangen, Germany. Department of Internal Medicine 5, Hematology and Oncology, Friedrich-Alexander-Universität Erlangen-Nürnberg and University Hospital Erlangen, Erlangen, GermanyVall d'Hebron Barcelona Hospital Campus202320232023info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttps://hdl.handle.net/11351/10382Scientiareponame:Scientia. Dipòsit d'Informació Digital del Departament de Salutinstname:Departament de Salut de la Generalitat de Catalunya (DS)InglésScience Advances;9(38)https://doi.org/10.1126/sciadv.adg3919Attribution-NonCommercial 4.0 Internationalhttp://creativecommons.org/licenses/by-nc/4.0/info:eu-repo/semantics/openAccessoai:scientiasalut.gencat.cat:11351/103822026-06-12T09:38:37Z
score 15.812455

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