Process data of allogeneic ex vivo - expanded ABCB5 + mesenchymal stromal cells for human use: off-the-shelf GMP-manufac
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(2020) 11:482
RESEARCH
Open Access
Process data of allogeneic ex vivoexpanded ABCB5+ mesenchymal stromal cells for human use: off-the-shelf GMPmanufactured donor-independent ATMP Seda Ballikaya1†, Samar Sadeghi1†, Elke Niebergall-Roth1†, Laura Nimtz1, Jens Frindert1, Alexandra Norrick1, Nicole Stemler1, Nicole Bauer1, Yvonne Rosche1, Vanessa Kratzenberg1, Julia Pieper1, Tina Ficek1, Markus H. Frank2,3,4,5, Christoph Ganss1,6, Jasmina Esterlechner1 and Mark A. Kluth1,6*
Abstract Background: Human dermal mesenchymal stromal cells (MSCs) expressing the ATP-binding cassette (ABC) efflux transporter ABCB5 represent an easily accessible MSC population that, based on preclinical and first-in-human data, holds significant promise to treat a broad spectrum of conditions associated not only with skin-related but also systemic inflammatory and/or degenerative processes. Methods: We have developed a validated Good Manufacturing Practice-compliant expansion and manufacturing process by which ABCB5+ MSCs derived from surgical discard skin tissues are processed to an advanced-therapy medicinal product (ATMP) for clinical use. Enrichment for ABCB5+ MSCs is achieved in a three-step process involving plastic adherence selection, expansion in a highly efficient MSC-selecting medium, and immunomagnetic isolation of the ABCB5+ cells from the mixed culture. Results: Product Quality Review data covering 324 cell expansions, 728 ABCB5+ MSC isolations, 66 ABCB5+ MSC batches, and 85 final drug products reveal high process robustness and reproducible, reliable quality of the manufactured cell therapy product. Conclusion: We have successfully established an expansion and manufacturing process that enables the generation of homogenous ABCB5+ MSC populations of proven biological activity manufactured as a standardized, donor-independent, highly pure, and highly functional off-the-shelf available ATMP, which is currently tested in multiple clinical trials. Keywords: Advanced-therapy medicinal product, ABCB5, GMP manufacturing, Mesenchymal stromal cells
* Correspondence: [email protected] † Seda Ballikaya, Samar Sadeghi and Elke Niebergall-Roth contributed equally to this work. 1 TICEBA GmbH, Im Neuenheimer Feld 517, 69120 Heidelberg, Germany 6 RHEACELL GmbH & Co. KG, Im Neuenheimer Feld 517, 69120 Heidelberg, Germany Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not perm
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