Project 2: Treating Advanced Ovarian Cancer Using Gene-Edited CAR NK Cells
In this research project, investigators in the Mayo Clinic Ovarian Cancer SPORE are exploring natural killer (NK) cells as an adoptive cellular therapy for cancer.
Natural killer cells have many favorable attributes. These attributes 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). However, developing these NK cells for clinical use has been slowed by difficulty expanding them to sufficient numbers, poor homing to tumors and persistence in tumors.
Building on previous work
This project builds on our 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 antitumor efficacy of NK cells in preclinical models.
Looking ahead
We're conducting a series of preclinical studies to further optimize CAR NK cell therapy. We also plan to conduct a phase 1 trial of the optimized cells in people with recurrent ovarian cancer.
Project co-leaders
University of Minnesota investigators Branden Moriarity, Ph.D.; Timothy Starr, Ph.D.; Melissa Geller, M.D., M.S.
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