Lessons Learned from Using TCR and CAR Gene Modified T Cells for Treating Cancer Patients

The recent FDA approval of various CAR, TCR, and TIL therapies has only increased the excitement over T cell based adoptive transfer therapies. We have manufactured TCR and CAR T cells to treat a total of 29 patients with melanoma (N=7), clear cell renal cell carcinoma (N=15), and non-Hodgkins lymphoma (N=7). While there were objective clinical responses in the three patient populations with the NHL patients treated with CD19 CAR T cells had the best outcomes. What is clear is that the genetically modified T cells can persist for years but they become nonfunctional, probably due to the host environment. Results from our trials support this notion and will be discussed with potential solutions to overcoming the immune suppressive tumor microenvironment.