Establishment of a simple and efficient platform for car-t cell generation and expansion: from lentiviral production to in vivo studies

建立简单有效的 CAR-T 细胞生成和扩增平台:从慢病毒生产到体内研究

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作者:Virgínia Picanço-Castro, Pablo Diego Moço, Amanda Mizukami, Leticia Delfini Vaz, Marcelo de Souza Fernandes Pereira, Renata Nacasaki Silvestre, Júlia Teixeira Cottas de Azevedo, Aline de Sousa Bomfim, Mario Soares de Abreu Neto, Kelen Cristina Ribeiro Malmegrim, Kamilla Swiech, Dimas Tadeu Covas

Conclusions

In this work, we show a high-level production of the lentiviral vector, which was successfully used to generate CAR-T cells. The CAR-T cells produced were highly cytotoxic and specific against CD19+ cells in vitro and in vivo, being able to fully control disease progression in a xenograft B-cell lymphoma mouse model. Our work demonstrates the feasibility of producing CAR-T cells in an academic context and can serve as a paradigm for similar institutions. Nevertheless, the results presented may contribute favoring the translation of the research to the clinical practice.

Methods

Our approach is based on a lentiviral vector composed by a second-generation CAR that signals through a 41BB and CD3-ζ endodomain. Conclusions: In this work, we show a high-level production of the lentiviral vector, which was successfully used to generate CAR-T cells. The CAR-T cells produced were highly cytotoxic and specific against CD19+ cells in vitro and in vivo, being able to fully control disease progression in a xenograft B-cell lymphoma mouse model. Our work demonstrates the feasibility of producing CAR-T cells in an academic context and can serve as a paradigm for similar institutions. Nevertheless, the

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