Engineering therapeutic probiotics to enhance GD2.CAR-T cell efficacy in pediatric solid tumors
Cancer treatment is quickly evolving from traditional chemotherapy to engineering our own cells as living medicines. With this momentum, I'm developing a new kind of cell therapy that brings together two unlikely partners: CAR-T cells - designer immune cells that target specific markers on cancer cells - and probiotics - ‘helpful bacteria’ that can selectively grow in solid tumors. CAR-T cells have cured children with certain blood cancers, but they’ve struggled in solid tumors like neuroblastoma and osteosarcoma where the hostile tumor environment, combined with the lack of ‘good’ markers to target, often shuts them down before they have a chance to work. Remarkably, the same harsh environment that weakens T cells can fuel the growth of some probiotic bacteria. These bacteria can be easily engineered to deliver custom-made signals and therapies directly inside the tumor. My research combines these complementary approaches - CAR-T cells and therapeutic bacteria - to create a more powerful treatment that fights solid tumors from the outside and in.
Project Goals
In my earlier work, I engineered bacteria to “paint” tumors with synthetic markers, making them easier for CAR-T cells to target and destroy. This worked – at first. But over time, too much additional stimulation from the bacteria eventually caused the CAR-T cells to burn out. To fix this, I’m redesigning the bacterial cell surface to be gentler on the immune system, making these microbes better partners for CAR-T cells and safer for young patients. To amplify these benefits for CAR-T cells, I am also engineering the bacteria to detect, and reverse, the inhibitory conditions created by tumors that shut down T cell activity. Finally, I will use advanced techniques to study how engineered bacteria, CAR-T cells, and the immune system interact inside tumors. Together, these efforts will lay the groundwork for a smarter, more cooperative therapy that could one day offer new hope to children with aggressive, difficult-to treat solid tumors.
