Process data of allogeneic ex vivo-expanded ABCB5+ mesenchymal stromal cells for human use: Off-the-shelf GMP-manufactured donor-independent ATMP

Authors/Creators

• Seda Ballikaya
• Samar Sadeghi
• Elke Niebergall-Roth
• Laura Nimtz
• Jens Frindert
• Alexandra Norrick
• Nicole Stemler
• Nicole Bauer
• Yvonne Rosche
• Vanessa Kratzenberg
• Julia Pieper
• Tina Ficek
• Markus H. Frank, Edith Cowan University
• Christoph Ganss
• Jasmina Esterlechner
• Mark A. Kluth

Abstract

© 2020, The Author(s). 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

ABCB5, Advanced-therapy medicinal product, GMP manufacturing, Mesenchymal stromal cells

Document Type

Journal Article

Date of Publication

2020

Volume

11

Issue

1

Publication Title

Stem Cell Research & Therapy

Publisher

Springer Nature

School

School of Medical and Health Sciences

RAS ID

35354

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 License.

Comments

Ballikaya, S., Sadeghi, S., Niebergall-Roth, E., Nimtz, L., Frindert, J., Norrick, A., ... Kluth, M. A. (2020). Process data of allogeneic ex vivo-expanded ABCB5+ mesenchymal stromal cells for human use: Off-the-shelf GMP-manufactured donor-independent ATMP. Stem Cell Research & Therapy, 11, article 482. https://doi.org/10.1186/s13287-020-01987-y