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Current challenges in providing good leukapheresis products for manufacturing of CAR-T cells for patients with relapsed/refractory NHL or ALL

Background: T lymphocyte collection through leukapheresis is an essential step for chimeric antigen receptor T (CAR-T) cell therapy. Timing of apheresis is challenging in heavily pretreated patients who suffer from rapid progressive disease and receive T cell impairing medication. Methods: A total o...

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Main Authors: Korell, Felix (Author) , Sauer, Sandra (Author) , Veelken, Kaya (Author) , Hennemann, Hannah Mai (Author) , Schubert, Maria-Luisa (Author) , Sauer, Tim (Author) , Müller-Tidow, Carsten (Author) , Dreger, Peter (Author) , Schmitt, Michael (Author) , Schmitt, Anita (Author)
Format: Article (Journal)
Language:English
Published: 15 May 2020
In: Cells
Year: 2020, Volume: 9, Issue: 5
ISSN:2073-4409
DOI:10.3390/cells9051225
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.3390/cells9051225
Verlag, lizenzpflichtig, Volltext: https://www.mdpi.com/2073-4409/9/5/1225
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Author Notes:Felix Korell, Sascha Laier, Sandra Sauer, Kaya Veelken, Hannah Hennemann, Maria-Luisa Schubert, Tim Sauer, Petra Pavel, Carsten Mueller-Tidow, Peter Dreger, Michael Schmitt, and Anita Schmitt
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Summary:Background: T lymphocyte collection through leukapheresis is an essential step for chimeric antigen receptor T (CAR-T) cell therapy. Timing of apheresis is challenging in heavily pretreated patients who suffer from rapid progressive disease and receive T cell impairing medication. Methods: A total of 75 unstimulated leukaphereses were analyzed including 45 aphereses in patients and 30 in healthy donors. Thereof, 41 adult patients with Non-Hodgkin’s lymphoma (85%) or acute lymphoblastic leukemia (15%) underwent leukapheresis for CAR-T cell production. Results: Sufficient lymphocytes were harvested from all patients even from those with low peripheral lymphocyte counts of 0.18/nL. Only four patients required a second leukapheresis session. Leukapheresis products contained a median of 98 × 108 (9 - 341 × 108) total nucleated cells (TNC) with 38 × 108 (4 - 232 × 108) CD3+ T cells. Leukapheresis products from healthy donors as well as from patients in complete remission were characterized by high TNC and CD3+ T lymphocyte counts. CAR-T cell products could be manufactured for all but one patient. Conclusions: Sufficient yield of lymphocytes for CAR-T cell production is feasible also for patients with low peripheral blood counts. Up to 12–15 L blood volume should be processed in patients with absolute lymphocyte counts ≤ 1.0/nL.
Item Description:Gesehen am 28.07.2020
Physical Description:Online Resource
ISSN:2073-4409
DOI:10.3390/cells9051225

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