CAR T cell therapy is a new kind of treatment for cancer and autoimmune disorders. To manufacture CAR T cell therapeutics, white blood cells are harvested from a patient's blood, genetically modified in a specialized manufacturing facility and frozen ready to be administered back to the patient. Because of immune rejection, attempts at mass-production "off-the-shelf" CAR T cell therapies have failed and the 5 FDA licensed CAR T cell therapies currently are autologous, requiring individualized manufacture from the patient's blood cells.
Despite the complexity of manufacture, the market for CAR T cell therapy continues to grow. Demand was initially from patients with lymphoma and leukemia which had not responded to conventional treatment but has extended to earlier lines of therapy in these diseases largely replacing stem cell transplantation. More recently, CAR T cell therapies have been approved for treating multiple myeloma. Recently, early clinical studies of CAR T cell therapy in autoimmune disorders suggest CAR T cells may be a revolutionary advance in treating autoimmune disorders which could increase market size by an order of magnitude.
The individualized nature of manufacture however results in a complex and significant environmental burden, particularly with plasticware and reagents. Commercial CAR T cell therapies are currently manufactured using a 7-10 day closed system macrofluidic manufacture process involving many discrete steps which include T cell isolation, T cell activation, transduction with a lentiviral vector, an expansion phase which allow the T cells to grow and finally, cryopreservation. Each one of these steps requires separate disposable culture systems / tubing kits and individual consumables such as magnetic separation beads / columns.
EcoCAR proposes to develop a CAR T cell manufacturing process that greatly reduces waste through a one-step / one-pot process. We plan to achieve this by exploiting engineering potential of the lentiviral vector which allows us to engineer viral particles which incorporate elements for T cell separation, activation, as well as gene-modification. Along with the use of this smart lentiviral vector, manufacture will be conducted in a single microfluidics system which allows manufacture in a single vessel using minimal volumes of culture media and other reagents.