Characterization of the Cytotoxic Activity of Natural Killer Cells on Spheroids

In recent decades, cancer therapy research has shifted from broad-spectrum treatments to specialized therapies that aim to treat individual cancer phenotypes. This shift led to the development of immunotherapies like CAR-T cell and CAR-NK cell therapy. This summer, we worked with Natural Killer cells (NK cells), determining their use in cancer therapy. NK cells act within the innate immune system, naturally targeting and destroying early stages of cancer development; however, more progressive stages of cancer evade NK cells. The purpose of this research project was to determine the relative efficacy of modified NK cell migration into tumors compared with wild-type NK cells. The experimental NK cells were modified with a surface protein that breaks adhesion bridges between cells, intending to assist NK cell infiltration into tumors. To test the benefit of adding this surface protein to NK cells, a spheroid model was used to simulate a tumor environment in vitro. With a co-incubation of NK cells and spheroids comprising PCI-13 and UPCI cancer cells, we set up several co-incubation conditions to determine the cytotoxic characteristics of NK cells and optimal co-incubation parameters. Flow cytometry and confocal microscopy were used to collect experimental data. The results showed that for different incubation periods are required for different cancer cell lines and that the addition of the surface protein was beneficial to NK cell migration. The results provide preliminary evidence to support further investigation into the use of modified NK cells in cancer therapy