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

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.