Yvonne Chen, Ph.D. 

Yvonne Chen, Ph.D., applies biomolecular engineering and synthetic biology techniques to make adoptive T-cell immunotherapies safer and more effective for the treatment of cancer. Adoptive T-cell immunotherapy is the process of engineering cancer patients’ own T cells (cells in the immune system) to fight cancer by equipping them with a cancer-recognizing receptor, known as a chimeric antigen receptor (CAR). The modified cells are then returned to the patient as a targeted therapy. This method has shown remarkable promise against multiple types of cancer.

One major obstacle to the broad application of this therapy is the inability to control the CAR-T cells from attacking healthy cells that display the same biochemical marker on their surface as tumor cells. Chen aims to overcome this hurdle by engineering CAR-T cells that use a two-step process to identify cancer cells. These next-generation CAR-T cells would identify cancer cells by their surface markers (similar to current methods), then deliver an engineered, conditionally active protein into those cells and seek a second tumor-associated signal. Only the cells that display both signals will be killed, thus sparing healthy cells.

Another potentially dangerous side effect of CAR-T therapy is cytokine release syndrome. All T cells naturally release cytokines, chemical messengers that help stimulate and direct immune response. In the case of cytokine release syndrome, a rapid and massive release of cytokines into the bloodstream can lead to dangerously high fevers and in some cases death. Chen and her lab are developing DNA-encoded circuits that enable T cells to rein in and prevent excessive cytokine production and signaling.

Solid tumors – tumors that grow as masses in the body – are difficult to treat because they have the ability to secrete proteins that suppress the immune system. For this reason, CAR-T therapies have shown a limited effect on solid tumors. In order to address this problem, the Chen lab engineered CAR-T cells that can detect tumors’ suppressive proteins and use them as a stimulant to trigger robust attacks on tumor cells. This approach enables T cells to convert solid tumors’ defense mechanism into a weapon that can be used to intensify the immune system’s attack on the tumor cells.

Chen earned her doctorate in chemical engineering from the California Institute of Technology and completed a post-doctoral fellowship in the department of systems biology at Harvard Medical School.