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

Autor: Wong DP; Department of Pathology, Case Western Reserve University, Cleveland, OH, USA., Roy NK; Division of Hematology/Oncology, Department of Medicine, Case Western Reserve University, Cleveland, OH, USA., Zhang K; Division of Hematology/Oncology, Department of Medicine, Case Western Reserve University, Cleveland, OH, USA., Anukanth A; Division of Pediatric Hematology/Oncology, Angie Fowler AYA Cancer Institute, UH Rainbow Babies & Children's Hospital, Cleveland, OH, USA., Asthana A; Division of Hematology/Oncology, Department of Medicine, Case Western Reserve University, Cleveland, OH, USA., Shirkey-Son NJ; Luminary Therapeutics, Minneapolis, MN, USA., Dunmire S; Luminary Therapeutics, Minneapolis, MN, USA., Jones BJ; Bio-Techne, Minneapolis, MN, USA., Lahr WS; Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA.; Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA.; Center for Genome Engineering, University of Minnesota, Minneapolis, MN, USA.; Stem Cell Institute, University of Minnesota, Minneapolis, MN, USA., Webber BR; Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA.; Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA.; Center for Genome Engineering, University of Minnesota, Minneapolis, MN, USA.; Stem Cell Institute, University of Minnesota, Minneapolis, MN, USA., Moriarity BS; Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA.; Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA.; Center for Genome Engineering, University of Minnesota, Minneapolis, MN, USA.; Stem Cell Institute, University of Minnesota, Minneapolis, MN, USA., Caimi P; Division of Hematology/Oncology, Department of Medicine, Case Western Reserve University, Cleveland, OH, USA.; The Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH, USA., Parameswaran R; Division of Hematology/Oncology, Department of Medicine, Case Western Reserve University, Cleveland, OH, USA. rxp278@case.edu.; The Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH, USA. rxp278@case.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2022 Jan 11; Vol. 13 (1), pp. 217. Date of Electronic Publication: 2022 Jan 11.
DOI: 10.1038/s41467-021-27853-w
Abstrakt: 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).)
Databáze: MEDLINE
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