Umbilical Cord Blood as a Source of Less Differentiated T Cells to Produce CD123 CAR-T Cells.

Chimeric Antigen Receptor (CAR) therapy has led to great successes in patients with leukemia and lymphoma. Umbilical Cord Blood (UCB), stored in UCB banks, is an attractive source of T cells for CAR-T production. We used a third generation CD123 CAR-T (CD28/4-1BB), which was previously developed using an adult's Peripheral Blood (PB), to test the ability of obtaining CD123 CAR-T from fresh or cryopreserved UCB. We obtained a cell product with a high and stable transduction efficacy, and a poorly differentiated phenotype of CAR-T cells, while retaining high cytotoxic functions in vitro and in vivo. Moreover, CAR-T produced from cryopreserved UCB are as functional as CAR-T produced from fresh UCB. Overall, these data pave the way for the clinical development of UCB-derived CAR-T. UCB CAR-T could be transferred in an autologous manner (after an UCB transplant) to reduce post-transplant relapses, or in an allogeneic setting, thanks to fewer HLA restrictions which ease the requirements for a match between the donor and recipient.