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.
© 2022. The Author(s).
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigens, CD / genetics
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Antigens, CD / immunology
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Antigens, Differentiation, T-Lymphocyte / genetics
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Antigens, Differentiation, T-Lymphocyte / immunology
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B-Cell Activating Factor / genetics*
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B-Cell Activating Factor / immunology
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B-Cell Activation Factor Receptor / genetics*
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B-Cell Activation Factor Receptor / immunology
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B-Cell Maturation Antigen / genetics*
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B-Cell Maturation Antigen / immunology
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B-Lymphocytes / immunology
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B-Lymphocytes / pathology
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Cell Line, Tumor
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Coculture Techniques
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Cytotoxicity, Immunologic
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Female
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Gene Expression Regulation, Neoplastic
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Humans
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Lectins, C-Type / genetics
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Lectins, C-Type / immunology
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Lymphocyte Activation
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Lymphoma, Mantle-Cell / genetics
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Lymphoma, Mantle-Cell / immunology
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Lymphoma, Mantle-Cell / pathology
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Lymphoma, Mantle-Cell / therapy*
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Lysosomal-Associated Membrane Protein 1 / genetics
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Lysosomal-Associated Membrane Protein 1 / immunology
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Male
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Mice
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Multiple Myeloma / genetics
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Multiple Myeloma / immunology
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Multiple Myeloma / pathology
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Multiple Myeloma / therapy*
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Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics
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Precursor Cell Lymphoblastic Leukemia-Lymphoma / immunology
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Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology
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Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy*
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Protein Binding
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Receptors, Chimeric Antigen / genetics
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Receptors, Chimeric Antigen / immunology
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Signal Transduction
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T-Lymphocytes / immunology
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T-Lymphocytes / transplantation
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Transmembrane Activator and CAML Interactor Protein / genetics*
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Transmembrane Activator and CAML Interactor Protein / immunology
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Xenograft Model Antitumor Assays
Substances
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Antigens, CD
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Antigens, Differentiation, T-Lymphocyte
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B-Cell Activating Factor
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B-Cell Activation Factor Receptor
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B-Cell Maturation Antigen
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CD69 antigen
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Lectins, C-Type
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Lysosomal-Associated Membrane Protein 1
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Receptors, Chimeric Antigen
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TNFRSF13B protein, human
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TNFRSF13C protein, human
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TNFRSF17 protein, human
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TNFSF13B protein, human
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Transmembrane Activator and CAML Interactor Protein