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Rejeski, K.* ; Perez, A.* ; Iacoboni, G.* ; Blumenberg, V.* ; Bücklein, V.L.* ; Völkl, S.* ; Penack, O.* ; Albanyan, O.* ; Stock, S.* ; Müller, F.* ; Karschnia, P.* ; Petrera, A. ; Reid, K.* ; Faramand, R.* ; Davila, M.L.* ; Modi, K.* ; Dean, E.A.* ; Bachmeier, C.* ; von Bergwelt-Baildon, M.* ; Locke, F.L.* ; Bethge, W.* ; Bullinger, L.* ; Mackensen, A.* ; Barba, P.* ; Jain, M.D.* ; Subklewe, M.*

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

Sci. Adv. 9:eadg3919 (2023)
Postprint DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Prolonged 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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Cytokine Release Syndrome; Stem-cell Boost; B-cell; Infectious Complications; Axicabtagene Ciloleucel; Interferon-gamma; Responses; Promotes; Interleukin-15; Inflammation
ISSN (print) / ISBN 2375-2548
e-ISSN 2375-2548
Zeitschrift Science Advances
Quellenangaben Band: 9, Heft: 38, Seiten: , Artikelnummer: eadg3919 Supplement: ,
Verlag American Association for the Advancement of Science (AAAS)
Verlagsort Washington, DC [u.a.]
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) CF Metabolomics & Proteomics (CF-MPC)
Förderungen Bavarian Cancer Research Center (BZKF)
ElseKroner-Fresenius Stiftung
Wilhelm-Sander Stiftung
Bavarian Elite Graduate Training Network
DFG
Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)
Bruno & Helene Joster Foundation
Gilead Research Scholar Program
Else Kroner Forschungskolleg (EKFK) within the Munich Clinician Scientist Program (MCSP)
School of Oncology of the German Cancer Consortium (DKTK)