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  • Title: A BAFF ligand-based CAR-T cell targeting three receptors and multiple B cell cancers.
    Author: Wong DP, Roy NK, Zhang K, Anukanth A, Asthana A, Shirkey-Son NJ, Dunmire S, Jones BJ, Lahr WS, Webber BR, Moriarity BS, Caimi P, Parameswaran R.
    Journal: Nat Commun; 2022 Jan 11; 13(1):217. PubMed ID: 35017485.
    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.
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