CAR T therapy, a therapeutic strategy to use the patient’s immune cells to fight cancer, has been promising with blood cancers but seems less effective in treating solid cancers. The SU2C–Lustgarten Foundation CAR T Research Team is using state-of-the-art epigenetic approaches and preclinical models to examine CAR T cells and tumor cells in patients who respond to CAR T therapy and in those who do not, with a particular focus on pancreatic cancer patients.