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Immobilized hematopoietic growth factors onto magnetic particles offer a scalable strategy for cell therapy manufacturing in suspension cultures

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journal contribution
posted on 10.01.2017, 14:02 authored by Matthew Worrallo, Rebecca L.L. Moore, Katie GlenKatie Glen, Rob ThomasRob Thomas
Hematopoietic therapies require high cell dosages and precise phenotype control for clinical success; scalable manufacturing processes therefore need to be economic and controllable, in particular with respect to culture medium and growth factor (GF) strategy. The aim of this work was to demonstrate the biological function, and integration within scalable systems, of a highly controllable immobilized growth factor (iGF) approach. GFs were biotinylated and attached to streptavidin coated magnetic particles. GF concentration during biotinylation, GF-biotin ratio, and GF lysine content were shown to control iGF surface concentration and enable predictable co-presentation of multiple GF on a single bead. Function was demonstrated for immobilized GMCSF, SCF, TPO and IL-3 in GF dependent cell lines TF-1 and M-07e. Immobilized GMCSF (iGMCSF) was analyzed to show sustained activity over eight days of culture, a two to three order of magnitude potency increase relative to soluble factor, and retained functionality under agitation in a microscale stirred tank bioreactor. Further, short exposure to iGMCSF demonstrated prolonged growth response relative to soluble factor. This immobilization approach has the potential to reduce the manufacturing costs of scaled cell therapy products by reducing GF quantities and offers important process control opportunities through separation of GF treatments from the bulk media.

History

School

  • Mechanical, Electrical and Manufacturing Engineering

Published in

Biotechnology Journal

Citation

WORRALLO, M.J., 2017. Immobilized hematopoietic growth factors onto magnetic particles offer a scalable strategy for cell therapy manufacturing in suspension cultures. Biotechnology Journal, 12 (2), article 1600493.

Publisher

© The Authors. Published by Wiley

Version

VoR (Version of Record)

Publisher statement

This work is made available according to the conditions of the Creative Commons Attribution 4.0 International (CC BY 4.0) licence. Full details of this licence are available at: http://creativecommons.org/licenses/ by/4.0/

Acceptance date

10/11/2016

Publication date

2017

Notes

This is an Open Access Article. It is published by Wiley under the Creative Commons Attribution 4.0 Unported Licence (CC BY). Full details of this licence are available at: http://creativecommons.org/licenses/by/4.0/

ISSN

1860-6768

Language

en