Gabriele Spohn, Eliza Wiercinska, Darja Karpova, Milica Bunos, Christiane Hümmer, Eva Wingenfeld, Nadine Sorg, Carolin Poppe, Volker Huppert, Juliane Stuth, Kristina Reck, Mike Essl, Erhard Seifried, Halvard-Björn Bönig
- 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.
MetadatenAuthor: | Gabriele SpohnORCiDGND, Eliza WiercinskaORCiDGND, Darja KarpovaORCiDGND, Milica Bunos, Christiane Hümmer, Eva Wingenfeld, Nadine Sorg, Carolin Poppe, Volker Huppert, Juliane Stuth, Kristina Reck, Mike Essl, Erhard SeifriedORCiDGND, Halvard-Björn BönigORCiDGND |
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URN: | urn:nbn:de:hebis:30:3-401372 |
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DOI: | https://doi.org/10.1016/j.jcyt.2015.04.005 |
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ISSN: | 1477-2566 |
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ISSN: | 1465-3249 |
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Pubmed Id: | https://pubmed.ncbi.nlm.nih.gov/25981397 |
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Parent Title (English): | Cytotherapy |
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Publisher: | Taylor & Francis Group |
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Place of publication: | Abington |
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Document Type: | Article |
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Language: | English |
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Year of Completion: | 2015 |
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Date of first Publication: | 2015/05/14 |
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Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
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Release Date: | 2017/02/06 |
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Tag: | CD34; CliniMACS; allogeneic; automation; cell therapy; clean room; good manufacturing practice; haplo-identical; immunomagnetic; naked haplo; stem cell transplantation |
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Volume: | 17 |
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Issue: | 10 |
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Page Number: | 7 |
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First Page: | 1465 |
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Last Page: | 1471 |
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Note: | https://creativecommons.org/licenses/by-nc-nd/4.0/ |
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HeBIS-PPN: | 453771378 |
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Institutes: | Medizin / Medizin |
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Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
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Sammlungen: | Universitätspublikationen |
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Licence (German): | Creative Commons - Namensnennung-Nicht kommerziell - Keine Bearbeitung 4.0 |
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