Yvonne Chen, Ph.D.

Yvonne Chen, Ph.D. 

Associate Professor, Microbiology, Immunology and Molecular Genetics; Chemical and Biomolecular Engineering

Bio

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-finding 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.

Honors & Affiliations

Honors

  • Excellence in Teaching Award, Northrop Grumman, 2017
  • Junior fellow, Harvard Society of Fellows

Affiliations

  • American Institute of Chemical Engineers
  • American Association for Cancer Research

 

Funding

Chen’s work is supported by the National Institutes of Health, Alliance for Cancer Gene Therapy, National Science Foundation, Parker Institute for Cancer Immunotherapy, the United States Department of Defense and the UCLA Broad Stem Cell Research Center, including support from The Rose Hills Foundation Innovator Grant.