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

• Published in: Cancers 2022-06, Vol.14 (13), p.3168
• Main Authors: Caël, Blandine, Galaine, Jeanne, Bardey, Isabelle, Marton, Chrystel, Fredon, Maxime, Biichle, Sabeha, Poussard, Margaux, Godet, Yann, Angelot-Delettre, Fanny, Barisien, Christophe, Bésiers, Christophe, Adotevi, Olivier, Pouthier, Fabienne, Garnache-Ottou, Francine, Bôle-Richard, Elodie
• Format: Article
• Language: English
• Subjects: Animal models; Antigens; Autografts; CD123 antigen; CD28 antigen; Cell differentiation; Chimeric antigen receptors; Cord blood; Cryopreservation; Cytokines; Cytotoxicity; Flow cytometry; Genotype & phenotype; Histocompatibility antigen HLA; Immunotherapy; Lymphocytes; Lymphocytes T; Lymphoma; Patients; Peripheral blood; Phenotypes; Proteins; Stem cells; Tumors; Umbilical cord
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers14133168

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.