Treating Advanced Ovarian Cancer Using Gene-Edited CAR NK Cells

In this research project, investigators in the Mayo Clinic Ovarian Cancer SPORE are collaborating on the exploration of natural killer (NK) cells as an adoptive cellular therapy for cancer.

The many favorable attributes of natural killer cells include their intrinsic ability to kill cancer cells without priming, their lower toxicity relative to T cells, and their potential for targeting through introduction of chimeric antigen receptors (CARs). Developing NK cells for clinical use has been slowed by the difficulty of expanding NK cells to sufficient numbers, poor homing to tumors and persistence in tumors.

This project builds on the project team's previous work, which has included:

• Conducting natural killer cell trials in ovarian cancer.
• Implementing methods for expanding NK cells on cytokine-expressing feeder layers.
• Developing methods for deleting the cytokine response inhibitory (CISH) gene in primary NK cells.
• Engineering an NK cell-specific CAR module that targets a tumor antigen present in most ovarian cancers.

Results from this work showed that these alterations enhance the persistence and anti-tumor efficacy of NK cells in preclinical models.

Investigators in this project are conducting a series of preclinical studies to further optimize CAR NK cell therapy. They also will conduct a phase 1 trial of the optimized cells in patients with recurrent ovarian cancer.