T cells redirected against Igß for the immunotherapy of B cell lymphoma.
Leukemia
; 34(3): 821-830, 2020 03.
Article
em En
| MEDLINE
| ID: mdl-31624374
ABSTRACT
CD19-redirected CAR-T immunotherapy has emerged as a promising strategy for treatment of B cell lymphoma, however, many patients often relapsed due to antigen loss. Therefore, it is urgently needed to explore other suitable antigens targeted by CAR-T cells to cure B cell lymphoma. Igß is a component of the B cell receptor (BCR) complex, which is highly expressed on the surface of lymphoma cells. In this study, we engineered T cells to express anti-Igß CAR with CD28 costimulatory signaling moiety and observed that Igß-CAR T cells could efficiently recognize and eliminate Igß+ lymphoma cells both in vitro and in two different lymphoma xenograft models. The specificity of Igß-CAR T cells was further confirmed through wild type or mutated Igß gene transduction together with Igß-specific knockout in target cells. Of note, both the in vitro and in vivo effect of Igß CAR-T cells was comparable with that of CD19 CAR-T cells. Importantly, Igß CAR-T cells recognized and eradicated patient-derived lymphoma cells in the autologous setting. Lastly, the safety of anti-Igß CAR-T cells could be further enhanced by introduction of the inducible caspase-9 suicide gene system. Collectively, Igß-specific CAR-T cells may be a promising immunotherapeutic approach for B cell lymphoma.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T
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Imunoterapia Adotiva
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Linfoma de Células B
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Antígenos CD79
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article