Located in the foothills of the Blue Ridge Mountains, our lab at the University of Virginia is dedicated to leveraging and strengthening the immune system to fight cancer. To do this, we use gene engineering to generate tumor-specific T cells, called chimeric antigen receptor T cells (CAR-T). This approach has revolutionized treatments for patients with blood cancers, resulting in ongoing curative responses for over a decade. Despite these promising results, CAR-T can be ineffective in patients with relapsed/refractory disease or solid tumors.

In the context of solid tumors, there are multiple contributing factors to the ineffective nature of CAR-T including lack of T cell trafficking, persistence and survival due in part to the immunosuppressive tumor microenvironment (TME). Our previous work highlights the need to strategically fuse basic immunology and synthetic biology to improve CAR-T safety and efficacy. The central focus of our research program is to identify and target drivers of intrinsic and extrinsic CAR-T resistance in patients with solid tumors, as well as to expand these findings to cell-based therapies beyond CAR-T. To this end, we will (I) identify genetic drivers of CAR-T efficacy and generate novel classic and invariant CAR-based cell therapies, (II) target the immunosuppressive TME and (III) design rational combination therapies with the ultimate goal of improving the lives of pediatric and adult cancer patients.