Developing novel strategies to enhance CAR Treg manufacture and testing in transplantation

After organ transplantation, patients must take immunosuppressive drugs to prevent rejection of the organ by their immune system. However, these drugs have severe side-effects. In contrast, regulatory T cell (Treg) therapy, which uses naturally suppressive immune cells to produce immunosuppression, can avoid these side-effects. Tregs for therapy can be isolated from patients, genetically modified in the lab, and infused back into patients to block unwanted immune responses without broader effects. However, improvements are still needed to this therapy. This project takes two strategies to enhance Treg therapy. Firstly, I will test the effect of supplementing lactic acid during cell growth in order to identify an optimal media composition that promotes function. Secondly, I will develop a human organ-in-a-dish system to model complicated transplantation immune responses in a lab without using mouse models, which often don’t replicate events in humans. Overall, this work will produce Tregs that function and survive better when administered to patients and develop a new way to test and model Treg function in a complex human system.