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Establishment of a simple and efficient platform for car-t cell generation and expansion: from lentiviral production to in vivo studies
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.
  • Picanço Castro, Virgínia; Universidade de São Paulo - USP. Hemocentro, Centro de Terapia Celular CTC. Ribeirão Preto. BR
  • Moço, Pablo Diego; Universidade de São Paulo - USP. Hemocentro, Centro de Terapia Celular CTC. Ribeirão Preto. BR
  • Mizukami, Amanda; Universidade de São Paulo - USP. Hemocentro, Centro de Terapia Celular CTC. Ribeirão Preto. BR
  • Vaz, Leticia Delfini; Universidade de São Paulo - USP. Hemocentro, Centro de Terapia Celular CTC. Ribeirão Preto. BR
  • Pereira, Marcelo de Souza Fernandes; Universidade de São Paulo - USP. Hemocentro, Centro de Terapia Celular CTC. Ribeirão Preto. BR
  • Silvestre, Renata Nacasaki; Universidade de São Paulo - USP. Hemocentro, Centro de Terapia Celular CTC. Ribeirão Preto. BR
  • Azevedo, Júlia Teixeira Cottas de; Universidade de São Paulo - USP. Hemocentro, Centro de Terapia Celular CTC. Ribeirão Preto. BR
  • Bomfim, Aline de Sousa; Universidade de São Paulo - USP. Hemocentro, Centro de Terapia Celular CTC. Ribeirão Preto. BR
  • Abreu Neto, Mario Soares de; Universidade de São Paulo - USP. Hemocentro, Centro de Terapia Celular CTC. Ribeirão Preto. BR
  • Malmegrim, Kelen Cristina Ribeiro; Universidade de São Paulo - USP. Hemocentro, Centro de Terapia Celular CTC. Ribeirão Preto. BR
  • Swiech, Kamilla; Universidade de São Paulo - USP. Hemocentro, Centro de Terapia Celular CTC. Ribeirão Preto. BR
  • Covas, Dimas Tadeu; Universidade de São Paulo - USP. Hemocentro, Centro de Terapia Celular CTC. Ribeirão Preto. BR
Hematol., Transfus. Cell Ther. (Impr.) ; 42(2): 150-158, Apr.-June 2020. tab, graf
Article in English | LILACS | ID: biblio-1134018
ABSTRACT
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.
Subject(s)


Full text: Available Index: LILACS (Americas) Main subject: In Vitro Techniques / Immunotherapy, Adoptive / Antigens, CD19 / Cytotoxicity, Immunologic / Heterografts Limits: Humans Language: English Journal: Hematol., Transfus. Cell Ther. (Impr.) Journal subject: Hematologia / TransfusÆo de Sangue Year: 2020 Type: Article Affiliation country: Brazil Institution/Affiliation country: Universidade de São Paulo - USP/BR

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Full text: Available Index: LILACS (Americas) Main subject: In Vitro Techniques / Immunotherapy, Adoptive / Antigens, CD19 / Cytotoxicity, Immunologic / Heterografts Limits: Humans Language: English Journal: Hematol., Transfus. Cell Ther. (Impr.) Journal subject: Hematologia / TransfusÆo de Sangue Year: 2020 Type: Article Affiliation country: Brazil Institution/Affiliation country: Universidade de São Paulo - USP/BR