IL-27-engineered CAR.19-NK-92 cells exhibit enhanced therapeutic efficacy

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) coexpre...

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Bibliographic Details
Published in:Cytotherapy (Oxford, England) England), 2024-06
Main Authors: 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
Format: Article
Language:English
Subjects:
blood cancer
CAR-NK
IL-27
immunotherapy
NK-92
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Summary: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. [Display omitted]
ISSN:1465-3249
1477-2566
1477-2566
DOI:10.1016/j.jcyt.2024.06.001