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Scale‐up of the ex vivo expansion of encapsulated primary human T lymphocytes
Author(s) -
Kaiser Patrick,
Werner Melanie,
Jérôme Valérie,
Freitag Ruth
Publication year - 2018
Publication title -
biotechnology and bioengineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.136
H-Index - 189
eISSN - 1097-0290
pISSN - 0006-3592
DOI - 10.1002/bit.26786
Subject(s) - ex vivo , laboratory flask , ammonium chloride , chemistry , t lymphocyte , bioreactor , chromatography , biochemistry , in vitro , organic chemistry
A number of evolving medical therapies call for the controlled expansion of primary human T lymphocytes. After encapsulation in sodium cellulose sulfate–poly(diallyldimethyl) ammonium chloride polyelectrolyte capsules, T lymphocytes can be expanded without persisting activation. Here, the challenge of scaling up this process is addressed. Encapsulated T lymphocytes were cultured in spinner flasks as well as in several types of the bioreactor, including fixed and fluidized beds, a waved cell bag, and a standard stirred tank reactor (STR; 1‐L scale). Two proprietary T lymphocyte culture media as well as a standard RPMI‐based medium were used. As before, encapsulation coincided with the presence of only a low fraction of activated T lymphocytes (peripheral blood T cells) in the total population. Unexpectedly, growth rates were lower in well‐mixed reactors than those in cultivations under static conditions, that is, in T‐flasks. Switching the STR to low oxygen conditions (40% air saturation) improved the growth rates to the level of the static cultures and thus forms the potential basis for efficient scale‐up of T lymphocyte expansion.