What is it?
Cancer is one of the leading causes of death both in the United States and worldwide. Recently, the field of immunotherapy has proven incredibly promising as a novel treatment method. Immunotherapy works by retargeting the immune system, which normally attacks invading pathogens such as bacteria or virally infected cells, to kill cancer cells instead. The power of immunotherapy lies in two main abilities: the fact that the immune system is capable of eradicating both a tumor and its distant metastases, which surgery and radiation are not able to do, and that immunological memory may prevent relapse of the cancer cells if they begin growing again. One type of immune cell that is known for its cancer cell-killing ability is the natural killer (NK) cell, but engineering these cells is difficult and as such there have not been many successful clinical trials using these cells against solid tumors yet.
I would like to engineer NK cells into tuneable cell therapeutics that can be combined with tumor-targeting antibodies to initiate an antitumor immune response in patients regardless of their genetic makeup or the profile of their tumor. I will do this by combining novel chimeric antigen receptors (CARs) with other activating receptors, as well as expressing activating molecules on feeder cells that can be used to cause the NK cells to proliferate and differentiate into even stronger killers. By designing a truly universal off-the-shelf cell therapeutic, I will be able to drastically decrease the cost of cell-based immunotherapy compared to the current CAR T cell production methods – this can cost almost half of a million dollars per patient and needs to be made on an individual basis, which also causes variability in the final product. By modulating both the feeder cells and the NK cells, I hope to create stronger immune synapses between the NK cells and the tumor cells they will target in patients and ideally improve clinical outcomes for patients with cancer.
What can it be used for?
The genes listed here can be expressed on NK cells, feeder cells, or tumor cells to study individual NK cell signaling pathways, strengths of activation of different receptor-ligand interactions, and whether certain NK cells are more or less resistant to inhibitory cues from cancer cells. These can all be combined in various combinations or used individually to assess synergistic effects as well. The CARs can be used to make NK cells that target surface molecules on B cells or any other cells, as long as an antibody or other targeting molecule can be designed against it.
Where can I find more information?
Designed By: Nina Horowitz, Stanford University