Vučinić Vladan, Tumewu Theresa, Brückner Mandy, Kirchberg Janine, Jentzsch Madlen, Buhmann Raymund, Remane Yvonne, Hoffmann Sandra, Ramdohr Florian, Merz Maximilian, Metzeler Klaus H, Schwind Sebastian, Herling Carmen, Krauß Simon M, Herling Marco, Franke Georg-Nikolaus, Grieb Nora, Stachel Georg, Janz Martin, Penack Olaf, Bullinger Lars, Keller Ulrich, Cross Michael, Henschler Reinhard, Bach Enrica, Platzbecker Uwe
Medical Clinic and Policlinic for Hematology, Cellular Therapy, Hemostaseology and Infectious Diseases, Leipzig University Medical Center, Leipzig, Germany.
Comprehensive Cancer Center Central Germany, Leipzig, Germany.
Transfusion. 2025 Sep;65(9):1650-1661. doi: 10.1111/trf.18354. Epub 2025 Jul 29.
Apheresis procedure of autologous lymphocytes competent for proliferation and expansion is a crucial step in the production of chimeric antigen receptor (CAR) T-cells. Previous therapies or disease status prior to collection may negatively impact the collections.
We performed a retrospective analysis with the aim to determine cellular factors in association with the collection of autologous T-cells and subsequent CAR T manufacturing toward tisagenlecleucel (tisa-cel). Between February 2019 and February 2022, 63 collections of 54 patients were performed for subsequent therapy with tisa-cel.
We observed no difference in median CD3+ cell yields according to the number of prior therapy lines (>3 vs. ≤3, p = .335), prior treatment with bendamustine (p = .954) or marrow infiltration (p = .634). Fifty-six collections were sent for manufacturing, of which 22 (39%) resulted in manufacturing failures, namely terminations (n = 12) or out-of-specification events (n = 10). Collections resulting in manufacturing failures yielded significantly lower CD3+ (p = .005), CD3+CD4+ (p = .044), and non-senescent CD3+CD27+CD28+ (p = .003) counts. Multivariable analysis identified the absolute number of CD3+CD27+CD28+ cells as relevant, with a calculated cut-off of ≥34.58 × 10 CD3+CD27+CD28+ cells for 89.5% probability of successful CAR T-cell production.
In summary, we report a positive influence of a higher number of non-senescent Τ-cells on successful manufacturing. Further analyses are required to determine measures for further optimization of collection outcomes.
对具有增殖和扩增能力的自体淋巴细胞进行单采程序是嵌合抗原受体（CAR）T细胞生产的关键步骤。采集前的既往治疗或疾病状态可能会对采集产生负面影响。
我们进行了一项回顾性分析，旨在确定与自体T细胞采集以及随后向替沙格韦单抗（tisagenlecleucel，tisa-cel）的CAR T制造相关的细胞因素。在2019年2月至2022年2月期间，对54例患者进行了63次采集，以便随后用tisa-cel进行治疗。
根据既往治疗线数（>3 vs.≤3，p = 0.335）、既往使用苯达莫司汀治疗（p = 0.954）或骨髓浸润（p = 0.634），我们观察到CD3 + 细胞中位数产量没有差异。56次采集被送去进行制造，其中22次（39%）导致制造失败，即终止（n = 12）或不符合规格事件（n = 10）。导致制造失败的采集产生的CD3 +（p = 0.005）、CD3 + CD4 +（p = 0.044）和非衰老CD3 + CD27 + CD28 +（p = 0.003）细胞计数显著更低。多变量分析确定CD3 + CD27 + CD28 + 细胞的绝对数量具有相关性，计算得出的临界值为≥34.58×10个CD3 + CD27 + CD28 + 细胞，成功生产CAR T细胞的概率为89.5%。
总之，我们报告了较高数量的非衰老T细胞对成功制造的积极影响。需要进一步分析以确定进一步优化采集结果的措施。
