Cytokines are proteins secreted by immune cells that stimulate immune responses against cancer and pathogens. However, their therapeutic efficacy is limited by their pleiotropic effects and systemic toxicity. My research focuses on manipulating cytokine responses to better treat immune disorders via engineered cytokine surrogate ligands with tailored activities. Our current work combines protein engineering, molecular immunology, and translational immunological mouse models to manipulate cytokine responses to better treat immune disorders by engineering cytokine surrogate ligands with tailored activities. We have shown that cytokine receptors can act as ‘rheostat’ and activate graded signalling responses upon alterations of their ligand-receptor binding parameters. By taking advantage of these findings, they have engineered surrogates of several cytokine systems and improved their clinical safety by reducing their functional pleiotropy. Thus, in realizing our fundamental objective of increasing the therapeutic efficacy of cytokine-based cancer therapy, we have constructed a molecular blueprint of biasing cytokine activity to boost anti-tumor response in the tumor microenvironment
In addition, I am also working on developing new cell therapies, such as Chimeric antigen receptor (CAR)-T or CAR-NK cells, on treating cancer and other diseases. CAR T-cell therapy has shown great promise in cancer treatment, but only a small percentage of patients respond. To improve the efficacy of CAR-T therapy, I am developing synthetic cytokine receptors that prolong the proliferative capacity of the CAR-T cells and enhance their activity in the tumor microenvironment. By doing so, I aim to increase the overall therapeutic activity of the therapy and fulfill its full potential as a promising cancer immunotherapy.