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A BAFF ligand-based CAR-T cell targeting three receptors and multiple B cell cancers

Author

Listed:
  • Derek P. Wong

    (Case Western Reserve University)

  • Nand K. Roy

    (Division of Hematology/Oncology, Department of Medicine, Case Western Reserve University)

  • Keman Zhang

    (Division of Hematology/Oncology, Department of Medicine, Case Western Reserve University)

  • Anusha Anukanth

    (Angie Fowler AYA Cancer Institute, UH Rainbow Babies & Children’s Hospital)

  • Abhishek Asthana

    (Division of Hematology/Oncology, Department of Medicine, Case Western Reserve University)

  • Nicole J. Shirkey-Son

    (Luminary Therapeutics)

  • Samantha Dunmire

    (Luminary Therapeutics)

  • Bryan J. Jones

    (Bio-Techne)

  • Walker S. Lahr

    (University of Minnesota
    Masonic Cancer Center, University of Minnesota
    Center for Genome Engineering, University of Minnesota
    Stem Cell Institute, University of Minnesota)

  • Beau R. Webber

    (University of Minnesota
    Masonic Cancer Center, University of Minnesota
    Center for Genome Engineering, University of Minnesota
    Stem Cell Institute, University of Minnesota)

  • Branden S. Moriarity

    (University of Minnesota
    Masonic Cancer Center, University of Minnesota
    Center for Genome Engineering, University of Minnesota
    Stem Cell Institute, University of Minnesota)

  • Paolo Caimi

    (Division of Hematology/Oncology, Department of Medicine, Case Western Reserve University
    The Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine)

  • Reshmi Parameswaran

    (Division of Hematology/Oncology, Department of Medicine, Case Western Reserve University
    The Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine)

Abstract

B cell-activating factor (BAFF) binds the three receptors BAFF-R, BCMA, and TACI, predominantly expressed on mature B cells. Almost all B cell cancers are reported to express at least one of these receptors. Here we develop a BAFF ligand-based chimeric antigen receptor (CAR) and generate BAFF CAR-T cells using a non-viral gene delivery method. We show that BAFF CAR-T cells bind specifically to each of the three BAFF receptors and are effective at killing multiple B cell cancers, including mantle cell lymphoma (MCL), multiple myeloma (MM), and acute lymphoblastic leukemia (ALL), in vitro and in vivo using different xenograft models. Co-culture of BAFF CAR-T cells with these tumor cells results in induction of activation marker CD69, degranulation marker CD107a, and multiple proinflammatory cytokines. In summary, we report a ligand-based BAFF CAR-T capable of binding three different receptors, minimizing the potential for antigen escape in the treatment of B cell cancers.

Suggested Citation

  • Derek P. Wong & Nand K. Roy & Keman Zhang & Anusha Anukanth & Abhishek Asthana & Nicole J. Shirkey-Son & Samantha Dunmire & Bryan J. Jones & Walker S. Lahr & Beau R. Webber & Branden S. Moriarity & Pa, 2022. "A BAFF ligand-based CAR-T cell targeting three receptors and multiple B cell cancers," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-021-27853-w
    DOI: 10.1038/s41467-021-27853-w
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    Cited by:

    1. Shuhong Li & Licai Shi & Lijun Zhao & Qiaoru Guo & Jun Li & Ze-lin Liu & Zhi Guo & Yu J. Cao, 2024. "Split-design approach enhances the therapeutic efficacy of ligand-based CAR-T cells against multiple B-cell malignancies," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

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