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 usi...

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Bibliographic Details
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
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Summary: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.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers14133168