Chimeric Antigen Receptor T Cells Targeting CD79b Show Efficacy in Lymphoma with or without Cotargeting CD19.
Clin Cancer Res
; 25(23): 7046-7057, 2019 12 01.
Article
em En
| MEDLINE
| ID: mdl-31439577
ABSTRACT
PURPOSE:
T cells engineered to express a chimeric antigen receptor (CAR) against CD19 have recently been FDA approved for the treatment of relapsed or refractory large B-cell lymphoma. Despite the success and curative potential of CD19 CAR T cells, several reports describing disease relapse due to antigen loss are now emerging. EXPERIMENTALDESIGN:
We developed a novel CAR construct directed against CD79b, a critical receptor for successful B-cell development that remains highly expressed in several subtypes of B-cell lymphoma, including mantle cell lymphoma (MCL). We tested CAR T cells directed against CD79b alone or in combination with CD19 targeting in a single construct, against cell line- and patient-derived xenograft models.RESULTS:
We demonstrate CAR79b antigen-specific recognition and cytotoxicity against a panel of cell lines and patient-derived xenograft models of MCL. Importantly, we show that downregulation of CD19 does not influence surface expression of CD79b and that anti-CD79b CAR T cells alone or arranged in a dual-targeting format with a CD19 single-chain variable fragment (scFv) are able to recognize and eliminate CD19+, CD19-, and mixed CD19+/CD19-B-cell lymphoma.CONCLUSIONS:
Our findings demonstrate that CAR T cells targeting CD79b alone or in combination have promise for treating and preventing CD19 antigen escape in B-cell lymphomas.
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Base de dados:
MEDLINE
Assunto principal:
Linfócitos T
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Imunoterapia Adotiva
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Antígenos CD19
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Linfoma de Célula do Manto
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Antígenos CD79
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Receptores de Antígenos Quiméricos
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article