A BAFF ligand-based CAR-T cell targeting three receptors and multiple B cell cancers.
Nat Commun
; 13(1): 217, 2022 01 11.
Article
en En
| MEDLINE
| ID: mdl-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.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Linfoma de Células del Manto
/
Factor Activador de Células B
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Receptor del Factor Activador de Células B
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Antígeno de Maduración de Linfocitos B
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Proteína Activadora Transmembrana y Interactiva del CAML
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Leucemia-Linfoma Linfoblástico de Células Precursoras
/
Mieloma Múltiple
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Nat Commun
Asunto de la revista:
BIOLOGIA
/
CIENCIA
Año:
2022
Tipo del documento:
Article