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CD20-bispecific antibodies improve response to CD19-CAR T cells in lymphoma in vitro and CLL in vivo models

Relapse after anti-CD19 chimeric antigen receptor (CD19-CAR) occurs in a substantial proportion of patients with lymphoid malignancies. We assessed the potential benefits of co-administering CD20-targeting bispecific antibodies (CD20-BsAbs) with CD19-CAR T cells with the aim of enhancing immunothera...

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Hauptverfasser: Brinkmann, Berit J. (VerfasserIn) , Floerchinger, Alessia (VerfasserIn) , Schniederjohann, Christina (VerfasserIn) , Roider, Tobias (VerfasserIn) , Coelho, Mariana (VerfasserIn) , Mack, Norman (VerfasserIn) , Bruch, Peter-Martin (VerfasserIn) , Liebers, Nora (VerfasserIn) , Dötsch, Sarah (VerfasserIn) , Busch, Dirk H. (VerfasserIn) , Schmitt, Michael (VerfasserIn) , Neumann, Frank (VerfasserIn) , Rößner, Philipp M. (VerfasserIn) , Seiffert, Martina (VerfasserIn) , Dietrich, Sascha (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: August 15, 2024
In: Blood
Year: 2024, Jahrgang: 144, Heft: 7, Pages: 784-789
ISSN:1528-0020
DOI:10.1182/blood.2023022682
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1182/blood.2023022682
Volltext
Verfasserangaben:Berit J. Brinkmann, Alessia Floerchinger, Christina Schniederjohann, Tobias Roider, Mariana Coelho, Norman Mack, Peter-Martin Bruch, Nora Liebers, Sarah Dötsch, Dirk H. Busch, Michael Schmitt, Frank Neumann, Philipp M. Roessner, Martina Seiffert, Sascha Dietrich
Beschreibung
Zusammenfassung:Relapse after anti-CD19 chimeric antigen receptor (CD19-CAR) occurs in a substantial proportion of patients with lymphoid malignancies. We assessed the potential benefits of co-administering CD20-targeting bispecific antibodies (CD20-BsAbs) with CD19-CAR T cells with the aim of enhancing immunotherapeutic efficacy. Addition of CD20-BsAbs to cocultures of CD19-CARs and primary samples of B-cell malignancies, comprising malignant B cells and endogenous T cells, significantly improved killing of malignant cells and enhanced the expansion of both endogenous T cells and CD19-CAR T cells. In an immunocompetent mouse model of chronic lymphocytic leukemia, relapse after initial treatment response frequently occurred after CD19-CAR T-cell monotherapy. Additional treatment with CD20-BsAbs significantly enhanced the treatment response and led to improved eradication of malignant cells. Higher efficacy was accompanied by improved T-cell expansion with CD20-BsAb administration and led to longer survival with 80% of the mice being cured with no detectable malignant cell population within 8 weeks of therapy initiation. Collectively, our in vitro and in vivo data demonstrate enhanced therapeutic efficacy of CD19-CAR T cells when combined with CD20-BsAbs in B-cell malignancies. Activation and proliferation of both infused CAR T cells and endogenous T cells may contribute to improved disease control.
Beschreibung:Gesehen am 24.10.2024
Beschreibung:Online Resource
ISSN:1528-0020
DOI:10.1182/blood.2023022682

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