TY  - JOUR
A1  - Spohn, Gabriele
A1  - Wiercinska, Eliza
A1  - Karpova, Darja
A1  - Bunos, Milica
A1  - Hümmer, Christiane
A1  - Wingenfeld, Eva
A1  - Sorg, Nadine
A1  - Poppe, Carolin
A1  - Huppert, Volker
A1  - Stuth, Juliane
A1  - Reck, Kristina
A1  - Essl, Mike
A1  - Seifried, Erhard
A1  - Bönig, Halvard-Björn
T1  - Automated CD34+ cell isolation of peripheral blood stem cell apheresis product
T2  - Cytotherapy
N2  - Background aims: Immunomagnetic enrichment of CD34+ hematopoietic “stem” cells (HSCs) using paramagnetic nanobead coupled CD34 antibody and immunomagnetic extraction with the CliniMACS plus system is the standard approach to generating T-cell-depleted stem cell grafts. Their clinical beneficence in selected indications is established. Even though CD34+ selected grafts are typically given in the context of a severely immunosuppressive conditioning with anti-thymocyte globulin or similar, the degree of T-cell depletion appears to affect clinical outcomes and thus in addition to CD34 cell recovery, the degree of T-cell depletion critically describes process quality. An automatic immunomagnetic cell processing system, CliniMACS Prodigy, including a protocol for fully automatic CD34+ cell selection from apheresis products, was recently developed. We performed a formal process validation to support submission of the protocol for CE release, a prerequisite for clinical use of Prodigy CD34+ products.
Methods: Granulocyte-colony stimulating factor–mobilized healthy-donor apheresis products were subjected to CD34+ cell selection using Prodigy with clinical reagents and consumables and advanced beta versions of the CD34 selection software. Target and non-target cells were enumerated using sensitive flow cytometry platforms.
Results: Nine successful clinical-scale CD34+ cell selections were performed. Beyond setup, no operator intervention was required. Prodigy recovered 74 ± 13% of target cells with a viability of 99.9 ± 0.05%. Per 5 × 10E6 CD34+ cells, which we consider a per-kilogram dose of HSCs, products contained 17 ± 3 × 10E3 T cells and 78 ± 22 × 10E3 B cells.
Conclusions: The process for CD34 selection with Prodigy is robust and labor-saving but not time-saving. Compared with clinical CD34+ selected products concurrently generated with the predecessor technology, product properties, importantly including CD34+ cell recovery and T-cell contents, were not significantly different. The automatic system is suitable for routine clinical application.
KW  - allogeneic
KW  - automation
KW  - cell therapy
KW  - clean room
KW  - CliniMACS
KW  - CD34
KW  - good manufacturing practice
KW  - haplo-identical
KW  - immunomagnetic
KW  - naked haplo
KW  - stem cell transplantation
Y1  - 2015
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/40137
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-401372
SN  - 1477-2566
SN  - 1465-3249
N1  - https://creativecommons.org/licenses/by-nc-nd/4.0/
VL  - 17
IS  - 10
SP  - 1465
EP  - 1471
PB  - Taylor & Francis Group
CY  - Abington
ER  -