Production of Clinical T Cell Therapies

The improving effectiveness of adoptive T cell therapies has led to their increased clinical application. Most of these adoptive T cell therapies are being produced in small lots in cell therapy centers affiliated with or located within academic health centers. Typically, the cells are produced from autologous or HLA compatible donors and one lot is used for a single patient. As part of early phase clinical trials, the best available methods and devices for the manufacture of clinical grade T cell therapies are described. For most adoptive T cell therapies the starting material is a peripheral blood mononuclear cell (PBMC) product that is collected by apheresis using closed system blood cell separators. Many manufacturing processes require that red blood cells be removed from the PBMCs or that T cells or T cell subsets are isolated. Classically, T cells have been cultured in flasks, but culture in closed systems which reduces the risk of microbial contamination is desirable and bags and bioreactors are often used for T cell culture and expansion. T cell culture involves growth and expansion in media supplemented with serum, cytokines and feeder cells or other artificial stimulators, i.e. anti-CD3/28 beads or K562 cell line. Recently, closed system transduction methods have been developed that can be used to produce genetically engineered T cells. Automated instruments are available to wash and concentrate products. The final product is assessed for the quantity of cells present, purity, sterility and potency. The use of these best practices is allowing for the consistent manufacturing of high quality cellular therapies to support early phase clinical trials.