In Vivo Generation of Chimeric Antigen Receptor Cells to Treat Hemopoietic Malignancies

CAR T-cell therapy has profoundly changed the standard of care for many cancers. For this treatment approach, a patient’s own T cells are extracted, genetically engineered to recognize and attack the cancer cells, and then expanded before administration back into the patient. Despite the impact and promise of CAR T-cell therapy, many challenges limit its use, mostly because the process of generating the CAR T cells is laborious, time-consuming, expensive, and must be tailored to each individual patient. For this project, Ron Levy and his group are developing a method to bypass the processing of CAR T cells outside of the patient, and instead, generate these cells within the patient’s own body. Using mice, they are utilizing novel polymeric materials to deliver messenger RNA encoding the chimeric T-cell receptors into immune cells in vivo to assess the uptake and effectiveness of this strategy. This work will pave the way not only to overcome the difficult steps of traditional CAR T cell generation but also to lay the groundwork for an “off-the-shelf” therapeutic option for patients with leukemias and lymphomas.