Generation of CMV-specific CD19 CAR T cells Using Cytokine Capture Followed by Lentiviral Transduction and Expansion
Lay Summary: Pediatric leukemia remains the second leading cause of cancer death in children. While outcomes for newly diagnosed patients have dramatically improved in the last several decades, response rates for relapsed ALL remain <50%. Chimeric antigen receptor (CAR) T cells are immune cells that are taken out of the body and genetically changed to attack cancer cells. CAR T cells are typically made from the patient’s own immune cells. The patient’s cells are affected by chemotherapy medications and can be both low in number and not function as well as a healthy person’s immune cells. For this reason, many patients are unable to receive this potentially lifesaving therapy because of manufacturing failures. Using donor immune cells can be dangerous because of the risk that they will attack the patient’s normal tissues.
Project Goal: Our goal is to use immune cells from the patient’s parent to make CAR T cells that will specifically target the leukemia cancer cells. The parental cells will be processed on a machine that selects out immune cells that are specific for a virus. These virus-specific cells do not cause graft versus host disease (GVHD). We will then generate CAR T cells from the virus-specific cells to be delivered to the patient. Successful funding of this project will allow the study investigators to generate the pre-clinical data required by the FDA before giving these experimental cells to patients.
Project Update 2023: Using a special peice of equipment, we selected out immune cells that are specific for a virus and do not cause GVHD. We then generated CAR T cells from the virus-specific cells to be delivered to the patient. We have successfully generated and grown these cells in the lab to large numbers, which will enable us to generate a large bank of donor virus specific CAR T cells for “off the shelf” use in the future. These cells are highly effective against leukemia cells in the lab and have minimal reactivity towards random donor cells in culture, which suggests that they would be safe and have a low risk of GVHD.
