The Then, Now, & Future of Engineered T-Cell Therapeutics for Human Application

Abstract

Since the 1990’s, we have conducted clinical trials of gene modified T cells. Chimeric antigen receptor (CAR) T cells independent of HLA and targeting CD19 on B cells leukemias and lymphomas have induced durable complete responses in patients who are relapsed or refractory to all other available treatments. New designs for genetically modified T cells include switches and potency enhancements that will be required for targeting solid tumors. In one such approach, a decoy receptor is inserted into CAR T cells to thwart a tumor immunosuppressive mechanism. Another improvement shortens ex vivo manufacturing, along with the addition of an anti-tumor cytokine to increase in vivo potency. Determining the critical quality attributes, dose, potency, and anticipating pharmacokinetics of a living, dividing drug presents unique challenges. Improving patient access to advanced cell and gene therapies entails not only on scientific progress in targeting, gene modification and cellular manipulation, but also on meeting automation, engineering, clinical site onboarding, and health policy challenges.