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

  • Blood. 2024 Aug 15;144(7):784-789. doi: 10.1182/blood.2023022682.
Berit J Brinkmann  1  2  3  4  5 ,  Alessia Floerchinger  5  6 ,  Christina Schniederjohann  1  2  5  7  8 ,  Tobias Roider  1  2  3 ,  Mariana Coelho  5  6 ,  Norman Mack  6 ,  Peter-Martin Bruch  1  2  7  8 ,  Nora Liebers  1  2  7  8  9 ,  Sarah Dötsch  10 ,  Dirk H Busch  10  11 ,  Michael Schmitt  1  12 ,  Frank Neumann  7 ,  Philipp M Roessner  6 ,  Martina Seiffert  6 ,  Sascha Dietrich  1  2  3  7  8
Affiliations
  • 1. Department of Medicine V, Hematology, Oncology and Rheumatology, University of Heidelberg, Heidelberg, Germany.
  • 2. Molecular Medicine Partnership Unit, Heidelberg, Germany.
  • 3. Genome Biology, European Molecular Biology Laboratory, Heidelberg, Germany.
  • 4. Clinical Cooperation Unit Molecular Hematology/Oncology, German Cancer Research Center, Heidelberg, Germany.
  • 5. Faculty of Biosciences, University of Heidelberg, Heidelberg, Germany.
  • 6. Molecular Genetics, German Cancer Research Center, Heidelberg, Germany.
  • 7. Department of Hematology, Oncology and Clinical Immunology, University Hospital Düsseldorf, Düsseldorf, Germany.
  • 8. Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf, Düsseldorf, Germany.
  • 9. Department of Translational Medical Oncology, National Center for Tumor Diseases, Heidelberg, Germany.
  • 10. Institute for Medical Microbiology, Immunology and Hygiene, Technical University of Munich, Munich, Germany.
  • 11. German Center for Infection Research, Partner Site Munich, Munich, Germany.
  • 12. German Cancer Consortium and German Cancer Research Center/National Center for Tumor Diseases, Heidelberg, Germany.
PMID: 38805637 DOI: 10.1182/blood.2023022682
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.