| Full text | |
| Author(s): Show less - |
Biggi, Alison Felipe Bordini
;
Silvestre, Renata Nacasaki
;
Tirapelle, Mariane Cariati
;
de Azevedo, Julia Teixeira Cottas
;
Garcia, Henry David Mogollo
;
dos Santos, Matheus Henrique
;
de Lima, Sarah Caroline Gomes
;
de Souza, Lucas Eduardo Botelho
;
Covas, Dimas Tadeu
;
Malmegrim, Kelen Cristina Ribeiro
;
Figueiredo, Marxa L.
;
Picanco-Castro, Virginia
Total Authors: 12
|
| Document type: | Journal article |
| Source: | CYTOTHERAPY; v. 26, n. 11, p. 11-pg., 2024-10-11. |
| 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. (c) 2024 International Society for Cell & Gene Therapy. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/) (AU) | |
| FAPESP's process: | 13/08135-2 - CTC - Center for Cell-Based Therapy |
| Grantee: | Dimas Tadeu Covas |
| Support Opportunities: | Research Grants - Research, Innovation and Dissemination Centers - RIDC |
| FAPESP's process: | 19/25309-0 - Off-the-shelf engineered NK cells for the treatment of Leukemia and Lymphoma treatment |
| Grantee: | Virginia Picanço e Castro |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 20/08279-8 - Establishment of a platform for generating NK-CAR cells with greater therapeutic effectiveness in vitro and in vivo |
| Grantee: | Júlia Teixeira Cottas de Azevedo |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |
| FAPESP's process: | 20/07055-9 - Nucleus of Cellular Therapy - NuTeC |
| Grantee: | Rodrigo do Tocantins Calado de Saloma Rodrigues |
| Support Opportunities: | Research Grants - Problem-Oriented Research Centers in São Paulo |