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| Item Type: | Article |
|---|---|
| Title: | Impact of cellular composition and T-cell senescence of mononuclear cell concentrates on the manufacturing process of chimeric antigen receptor (CAR) T-cells |
| Creators Name: | 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 and Platzbecker, Uwe |
| Abstract: | BACKGROUND: 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. STUDY DESIGN AND METHODS: 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. RESULTS: 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(8) CD3+CD27+CD28+ cells for 89.5% probability of successful CAR T-cell production. DISCUSSION: 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. |
| Keywords: | Apheresis Procedure, CAR T-cells, Out-of-Specification Events |
| Source: | Transfusion |
| ISSN: | 0041-1132 |
| Publisher: | Wiley / AABB |
| Page Range: | 1-12 |
| Date: | 29 July 2025 |
| Official Publication: | https://doi.org/10.1111/trf.18354 |
| PubMed: | View item in PubMed |
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