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

AUTOR(ES)

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

FONTE

Hematol., Transfus. Cell Ther.

DATA DE PUBLICAÇÃO

2020-06

RESUMO

ABSTRACT Introduction: Adoptive transfer of T cells expressing a CD19-specific chimeric antigen receptor (CAR) has shown impressive response rates for the treatment of CD19 + B-cell malignancies in numerous clinical trials. The CAR molecule, which recognizes cell-surface tumor-associated antigen independently of human leukocyte antigen (HLA), is composed by one or more signaling molecules to activate genetically modified T cells for killing, proliferation, and cytokine production. Objectives: In order to make this treatment available for a larger number of patients, we developed a simple and efficient platform to generate and expand CAR-T cells. 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 results presented may contribute favoring the translation of the research to the clinical practice.

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