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

被引:16
作者
Cael, Blandine [1 ]
Galaine, Jeanne [1 ]
Bardey, Isabelle [2 ]
Marton, Chrystel [1 ,3 ]
Fredon, Maxime [1 ]
Biichle, Sabeha [1 ]
Poussard, Margaux [1 ]
Godet, Yann [1 ]
Angelot-Delettre, Fanny [1 ,4 ]
Barisien, Christophe [5 ]
Besiers, Christophe [4 ]
Adotevi, Olivier [1 ,6 ]
Pouthier, Fabienne [2 ]
Garnache-Ottou, Francine [1 ]
Bole-Richard, Elodie [1 ]
机构
[1] Univ Bourgogne Franche Comte, RIGHT Interact Greffon Hote Tumeur Ingenierie Cel, EFS BFC, INSERM, F-25000 Besancon, France
[2] Etab Francais Sang Bourgogne Franche Comte, Act Ingn Cellulaire & Tissulaire, F-25000 Besancon, France
[3] CHU Lille, Dept Hematol, Allogen Stem Cell Transplantat Unit, F-59000 Lille, France
[4] EFS Bourgogne Franche Comte, F-25000 Besancon, France
[5] Etab Francais Sang Bourgogne Franche Comte, Dept Collecte & Prod PSL, F-25000 Besancon, France
[6] CHU Besancon, Serv Oncol Med, F-25000 Besancon, France
关键词
Umbilical Cord Blood; CAR-T cells; adoptive cell therapy; allogeneic immunotherapy; CD123; ADULT PERIPHERAL-BLOOD; MEMORY STEM-CELLS; IMMUNOTHERAPY; 4-1BB; CD28; IL-7; COSTIMULATION; SPECIFICITY; THERAPY;
D O I
10.3390/cancers14133168
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Simple Summary We used fresh or thawed Umbilical Cord Blood (UCB) to produce CAR-T cells directed against CD123, and we compared their functionality to Peripheral Blood (PB) CAR-T cells. T cells expressing CD123 CAR, derived from UCB, was exhibited through a high transduction rate, activation status, and cytotoxic potential in vitro as PB derived CAR-T cells. Moreover, we obtained T cells that had a less differentiated profile than the PB-derived T cells. UCB derived CAR-T can significantly control tumor progression in mice models. CAR-T obtained from thawed or fresh UCB gives the same results. 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.
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页数:16
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