During HCT, donor immune cells will attack and kill recipient tumor (or leukemia) cells in ways that are not completely understood. However, donor T cells with specificity for tumor can eventually lose their tumor killing properties or fail to expand their numbers sufficiently. With our collaborators in the Bleakley and Hill labs, we are working to understand these failures more deeply.

Adoptive T cell therapy is an exciting new direction in the treatment of malignancy. T cells can be harvested from a patient and genetically engineered with specificity for tumor. Although adoptive cellular therapies such as chimeric antigen receptors (CARs) and transgeneic T cell receptors (TCRs) have shown promise clinically, there remain a number of barriers to greater success. Together with our collaborators in the Riddell lab we are using genomic technologies, some of which were developed by the Henikoff lab, to dissect the gene regulatory landscape of genetically modified and expanded T cell products. We believe with a deeper understanding of the transcriptional events that take place early in T cell activation and expansion, we will be able to embue the next generation of adoptive T cell therapies with better memory, potency, and longevity.