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
RIGHT Interactions Greffon-Hôte-Tumeur/Ingénierie Cellulaire et Génique, EFS BFC, INSERM, Univ. Bourgogne Franche-Comté, F-25000 Besançon, France.
Activité d'Ingénierie Cellulaire et Tissulaire, Etablissement Français du Sang Bourgogne/Franche-Comté, F-25000 Besançon, France.
Cancers (Basel). 2022 Jun 28;14(13):3168. 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.
嵌合抗原受体（CAR）疗法已在白血病和淋巴瘤患者中取得了巨大成功。储存在脐带血库中的脐带血（UCB）是用于生产CAR-T的T细胞的一个有吸引力的来源。我们使用了第三代CD123 CAR-T（CD28/4-1BB），其先前是使用成人外周血（PB）开发的，以测试从新鲜或冷冻保存的UCB中获得CD123 CAR-T的能力。我们获得了一种具有高且稳定转导效率以及CAR-T细胞低分化表型的细胞产品，同时在体外和体内均保留了高细胞毒性功能。此外，由冷冻保存的UCB产生的CAR-T与由新鲜UCB产生的CAR-T具有相同的功能。总体而言，这些数据为UCB来源的CAR-T的临床开发铺平了道路。UCB CAR-T可以以自体方式（在UCB移植后）进行移植以减少移植后复发，或者在同种异体环境中进行移植，这得益于较少的HLA限制，从而放宽了对供体和受体之间匹配的要求。
