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IL-27-engineered CAR.19-NK-92 cells exhibit enhanced therapeutic efficacy.
Biggi, Alison Felipe Bordini; Silvestre, Renata Nacasaki; Tirapelle, Mariane Cariati; de Azevedo, Julia Teixeira Cottas; García, Henry David Mogollón; Henrique Dos Santos, Matheus; de Lima, Sarah Caroline Gomes; de Souza, Lucas Eduardo Botelho; Covas, Dimas Tadeu; Malmegrim, Kelen Cristina Ribeiro; Figueiredo, Marxa L; Picanço-Castro, Virginia.
Afiliação
  • Biggi AFB; Center for Cell-based Therapy CTC, Regional Blood Center of Ribeirão Preto, University of São Paulo, São Paulo, Brazil.
  • Silvestre RN; Center for Cell-based Therapy CTC, Regional Blood Center of Ribeirão Preto, University of São Paulo, São Paulo, Brazil.
  • Tirapelle MC; Center for Cell-based Therapy CTC, Regional Blood Center of Ribeirão Preto, University of São Paulo, São Paulo, Brazil.
  • de Azevedo JTC; Center for Cell-based Therapy CTC, Regional Blood Center of Ribeirão Preto, University of São Paulo, São Paulo, Brazil; Department of Hemotherapy and Cellular Therapy, Hospital Israelita Albert Einstein, São Paulo, Brazil.
  • García HDM; Universidade Estadual de Campinas, Instituto de Biologia, São Paulo, Brazil.
  • Henrique Dos Santos M; Center for Cell-based Therapy CTC, Regional Blood Center of Ribeirão Preto, University of São Paulo, São Paulo, Brazil.
  • de Lima SCG; Center for Cell-based Therapy CTC, Regional Blood Center of Ribeirão Preto, University of São Paulo, São Paulo, Brazil.
  • de Souza LEB; Center for Cell-based Therapy CTC, Regional Blood Center of Ribeirão Preto, University of São Paulo, São Paulo, Brazil.
  • Covas DT; Center for Cell-based Therapy CTC, Regional Blood Center of Ribeirão Preto, University of São Paulo, São Paulo, Brazil.
  • Malmegrim KCR; Center for Cell-based Therapy CTC, Regional Blood Center of Ribeirão Preto, University of São Paulo, São Paulo, Brazil; Department of Clinical Analyses, Toxicology and Food Science, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil.
  • Figueiredo ML; Department of Basic Medical Sciences, Purdue University, West Lafayette, Indiana, USA.
  • Picanço-Castro V; Center for Cell-based Therapy CTC, Regional Blood Center of Ribeirão Preto, University of São Paulo, São Paulo, Brazil. Electronic address: virginia.picanco@hemocentro.fmrp.usp.br.
Cytotherapy ; 2024 Jun 06.
Article em En | MEDLINE | ID: mdl-38970613
ABSTRACT
Chimeric antigen receptor (CAR) engineering of natural killer (NK) cells has shown promising results in early-phase clinical studies. However, advancing CAR-NK cell therapeutic efficacy is imperative. In this study, we investigated the impact of a fourth-generation CD19-targeted CAR (CAR.19) coexpressing IL-27 on NK-92 cells. We observed a significant improvement in NK-92 cell proliferation and cytotoxicity activity against B-cell cancer cell lines, both in vitro and in a xenograft mouse B-cell lymphoma model. Our systematic transcriptome analysis of the activated NK-92 CAR variants further supports the potential of IL-27 in fourth-generation CARs to overcome limitations of NK cell-based targeted tumor therapies by providing essential growth and activation signals. Integrating IL-27 into CAR-NK cells emerges as a promising strategy to enhance their therapeutic potential and elicit robust responses against cancer cells. These findings contribute substantially to the mounting evidence supporting the potential of fourth-generation CAR engineering in advancing NK cell-based immunotherapies.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Cytotherapy Assunto da revista: TERAPEUTICA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Brasil País de publicação: Reino Unido

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Cytotherapy Assunto da revista: TERAPEUTICA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Brasil País de publicação: Reino Unido