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Updated: Jun 21, 2025
Natural Killer NK and CAR-NK Cell Expansion Method using Membrane Bound-IL-21-Modified B Cell Line
Published on: February 8, 2022
IL-27-engineered CAR.19-NK-92 cells exhibit enhanced therapeutic efficacy
Alison Felipe Bordini Biggi1, Renata Nacasaki Silvestre1, Mariane Cariati Tirapelle1
1Center for Cell-based Therapy CTC, Regional Blood Center of Ribeirão Preto, University of São Paulo, São Paulo, Brazil.
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.
Insights
Engineered natural killer (NK) cells with a novel chimeric antigen receptor (CAR) demonstrated enhanced anti-cancer activity. Co-expressing IL-27 improved NK cell proliferation and killing of B-cell cancers, advancing targeted immunotherapies.
Area of Science:
- Immunotherapy
- Cellular Therapy
- Oncology
Background:
- Chimeric antigen receptor (CAR) engineering of natural killer (NK) cells shows promise in early clinical trials.
- Enhancing the therapeutic efficacy of CAR-NK cells is crucial for advancing cancer treatments.
- Limitations exist in current NK cell-based targeted tumor therapies.
Purpose of the Study:
- To investigate the impact of a fourth-generation CD19-targeted CAR (CAR.19) coexpressing IL-27 on NK-92 cells.
- To evaluate the potential of IL-27 integration in CAR-NK cells for improved anti-cancer responses.
Main Methods:
- Engineering NK-92 cells with a fourth-generation CD19-targeted CAR (CAR.19) coexpressing IL-27.
- In vitro assessment of NK-92 CAR variant proliferation and cytotoxicity against B-cell cancer lines.
- In vivo evaluation in a xenograft mouse B-cell lymphoma model.
- Systematic transcriptome analysis of activated NK-92 CAR variants.
Main Results:
- Significant improvement in NK-92 CAR.19 cell proliferation and cytotoxicity against B-cell cancer cell lines.
- Enhanced anti-tumor activity observed both in vitro and in a xenograft mouse B-cell lymphoma model.
- Transcriptome analysis revealed IL-27 provides essential growth and activation signals.
Conclusions:
- Integrating IL-27 into fourth-generation CAR-NK cells significantly enhances their therapeutic potential.
- IL-27 coexpression overcomes limitations in NK cell-based targeted tumor therapies by providing growth and activation signals.
- This strategy represents a promising advancement for NK cell-based immunotherapies against cancer.
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