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

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, Paolo Caimi and Reshmi Parameswaran ()
Additional contact information
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
Beau R. Webber: University of Minnesota
Branden S. Moriarity: University of Minnesota
Paolo Caimi: Division of Hematology/Oncology, Department of Medicine, Case Western Reserve University
Reshmi Parameswaran: Division of Hematology/Oncology, Department of Medicine, Case Western Reserve University

Nature Communications, 2022, vol. 13, issue 1, 1-17

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-021-27853-w

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