Fig. 6.

Manufacturing and delivery pipeline of genetically modified T-cell therapies. (i) T cells are harvested from a patient and sent to a good manufacturing practices (GMP) manufacturing facility, which might not be local to the treating hospital. Cells that pass acceptance criteria are genetically engineered (ii) with either a new T cell receptor (TCR) or a receptor based on a recognition sequence of an antibody [chimeric antigen receptor (CAR)], combined with T-cell co-stimulatory sequences. After a brief period of in vitro expansion and passing of product-specific release criteria (iii), the T-cell product must be returned to the correct patient (iv). The patient can undergo conditioning regimens prior to infusion of the genetically modified T-cell product (v). The complexity of this multi-step process in the manufacture and delivery of T-cell immunotherapies poses several economic and regulatory issues, which represent a challenge for the improvement and accessibility of such therapies. PBMC, peripheral blood mononuclear cell.