Engineering natural killer cells to target ovarian cancer tumors via metabolite-sensing receptors

Project summary

Immune cells have the remarkable ability to detect and kill cancer cells. However, for that killing to occur the immune cells need to be in direct physical contact with the cancer cells. We thus reasoned that if we could find ways to engineer immune cells in a way that will mobilize them to reach and persist within ovarian cancer tumors this could form a new cell therapy for ovarian cancer patients, where these engineered immune cells will be used as living drugs . We performed large experiments where we engineered immune cells in thousands of different ways and let these cells compete against each other, allowing us to identify those that were best at reaching ovarian cancer tumors in mice. These powerful experiments uncovered a new and effective mechanism to recruit immune cells to the tumor. Here we will use immune cell engineering and advanced molecular and genetic tools to determine how this novel mechanism of immune recruitment works. We will conduct rigorous experiments to test if this new immune cell engineering treatment strategy can safely eradicate ovarian cancer tumors in mice. We will also begin testing whether this treatment is able to generate immune memory so that the entire immune system will continue to be on the lookout to avoid disease recurrence and obtain durable responses. If successful, it will introduce and new paradigm for immune recruitment and provide a basis for a new cell therapy for the treatment of ovarian cancer.