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Related Experiment Video

Updated: Dec 29, 2025

Flow Cytometry-based Assay for the Monitoring of NK Cell Functions

Flow Cytometry-based Assay for the Monitoring of NK Cell Functions

Published on: October 30, 2016

Selective and Potent CDK8/19 Inhibitors Enhance NK-Cell Activity and Promote Tumor Surveillance.

Marco H Hofmann¹, Rajeswaran Mani², Harald Engelhardt³

¹Boehringer Ingelheim RCV GmbH & Co KG, Vienna, Austria. marco.hofmann@boehringer-ingelheim.com.

Molecular Cancer Therapeutics

|February 7, 2020

Summary

New CDK8/19 inhibitors enhance natural killer (NK) cell function, boosting anti-cancer immunity. This approach improves survival in preclinical cancer models and potentiates immunotherapy, offering a novel strategy for solid tumor treatment.

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Isolation and Expansion of Cytotoxic Cytokine-induced Killer T Cells for Cancer Treatment

Isolation and Expansion of Cytotoxic Cytokine-induced Killer T Cells for Cancer Treatment

Published on: January 24, 2020

Area of Science:

Immunology
Molecular Biology
Oncology

Background:

Natural killer (NK) cells are crucial for cancer control, with their activation tightly regulated by signaling pathways.
Cyclin-dependent kinases 8 and 19 (CDK8/19) are identified as signaling intermediates within NK cells.

Purpose of the Study:

To investigate the therapeutic potential of CDK8/19 inhibitors in modulating NK cell activity.
To evaluate the efficacy of CDK8/19 inhibition in enhancing NK cell-mediated cancer cell lysis and in vivo anti-tumor responses.

Main Methods:

Development and application of CDK8/19 inhibitors to suppress STAT1 phosphorylation in NK cells.
Assessment of perforin and granzyme B production and NK cell-mediated lysis of leukemia cells.
Evaluation of CDK8/19 inhibitor BI-1347 in mouse models of melanoma and breast cancer xenografts.
Combination therapy studies with anti-PD-1 antibodies and SMAC mimetics.

Main Results:

CDK8/19 inhibition augmented perforin and granzyme B production, enhancing NK cell-mediated lysis of leukemia cells.
BI-1347 treatment improved response rates and survival in mice with melanoma and breast cancer xenografts.
Combined treatment with BI-1347 and SMAC mimetic BI-8382 significantly increased survival in an EMT6 breast cancer model, dependent on intermittent BI-1347 dosing.

Conclusions:

CDK8/19 inhibitors represent a promising strategy to enhance NK cell function and anti-tumor immunity.
Intermittent dosing of CDK8/19 inhibitors may be crucial for sustained NK cell responsiveness.
Combining CDK8/19 inhibitors with adaptive immune modulators offers a novel approach for treating solid tumors by boosting NK cell activity.