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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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Main Authors: Brinkmann, Berit J. (Author) , Floerchinger, Alessia (Author) , Schniederjohann, Christina (Author) , Roider, Tobias (Author) , Coelho, Mariana (Author) , Mack, Norman (Author) , Bruch, Peter-Martin (Author) , Liebers, Nora (Author) , Dötsch, Sarah (Author) , Busch, Dirk H. (Author) , Schmitt, Michael (Author) , Neumann, Frank (Author) , Rößner, Philipp M. (Author) , Seiffert, Martina (Author) , Dietrich, Sascha (Author)
Format: Article (Journal)
Language:English
Published: August 15, 2024
In: Blood
Year: 2024, Volume: 144, Issue: 7, Pages: 784-789
ISSN:1528-0020
DOI:10.1182/blood.2023022682
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1182/blood.2023022682
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Author Notes: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
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Summary: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.
Item Description:Gesehen am 24.10.2024
Physical Description:Online Resource
ISSN:1528-0020
DOI:10.1182/blood.2023022682

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