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CD20-bispecific antibodies improve response to CD19-CAR T cells in lymphoma in vitro and CLL in vivo models.
Brinkmann, Berit J; Floerchinger, Alessia; Schniederjohann, Christina; Roider, Tobias; Coelho, Mariana; Mack, Norman; Bruch, Peter-Martin; Liebers, Nora; Dötsch, Sarah; Busch, Dirk H; Schmitt, Michael; Neumann, Frank; Roessner, Philipp M; Seiffert, Martina; Dietrich, Sascha.
Afiliación
  • Brinkmann BJ; Department of Medicine V, Hematology, Oncology and Rheumatology, University of Heidelberg, Heidelberg, Germany.
  • Floerchinger A; Molecular Medicine Partnership Unit, Heidelberg, Germany.
  • Schniederjohann C; Genome Biology, European Molecular Biology Laboratory, Heidelberg, Germany.
  • Roider T; Clinical Cooperation Unit Molecular Hematology/Oncology, German Cancer Research Center, Heidelberg, Germany.
  • Coelho M; Faculty of Biosciences, University of Heidelberg, Heidelberg, Germany.
  • Mack N; Faculty of Biosciences, University of Heidelberg, Heidelberg, Germany.
  • Bruch PM; Molecular Genetics, German Cancer Research Center, Heidelberg, Germany.
  • Liebers N; Department of Medicine V, Hematology, Oncology and Rheumatology, University of Heidelberg, Heidelberg, Germany.
  • Dötsch S; Molecular Medicine Partnership Unit, Heidelberg, Germany.
  • Busch DH; Faculty of Biosciences, University of Heidelberg, Heidelberg, Germany.
  • Schmitt M; Department of Hematology, Oncology and Clinical Immunology, University Hospital Düsseldorf, Düsseldorf, Germany.
  • Neumann F; Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf, Düsseldorf, Germany.
  • Roessner PM; Department of Medicine V, Hematology, Oncology and Rheumatology, University of Heidelberg, Heidelberg, Germany.
  • Seiffert M; Molecular Medicine Partnership Unit, Heidelberg, Germany.
  • Dietrich S; Genome Biology, European Molecular Biology Laboratory, Heidelberg, Germany.
Blood ; 144(7): 784-789, 2024 Aug 15.
Article en En | MEDLINE | ID: mdl-38805637
ABSTRACT
ABSTRACT 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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Leucemia Linfocítica Crónica de Células B / Inmunoterapia Adoptiva / Anticuerpos Biespecíficos / Antígenos CD20 / Antígenos CD19 Límite: Animals / Humans Idioma: En Revista: Blood Año: 2024 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Leucemia Linfocítica Crónica de Células B / Inmunoterapia Adoptiva / Anticuerpos Biespecíficos / Antígenos CD20 / Antígenos CD19 Límite: Animals / Humans Idioma: En Revista: Blood Año: 2024 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos