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P23

Scalable generation and tailored design of human iPSC-derived macrophages for novel immunotherapies

M Ackermann¹   A Rafiei Hashtchin¹   M Schinke¹   G Meyer¹   L Bach¹ ⁴   M Hetzel¹   F Manstein¹   B Fehlhaber¹   H Kempf¹ ³   A Schambach¹ ²   R Zweigerdt¹   G Hansen¹   D Viemann¹ ⁵   A Munder¹ ⁶  N Lachmann¹ ⁶

1:Hannover Medical School;   2:Harvard Medical School;   3:Novo Nordisk;   4:Universitätsklinikum Bonn;   5:University Hospital Würzburg;   6:German Center for Lung Research (DZL, BREATH)

Macrophages possess a unique potential to initiate and modulate immune reactions. Therefore, seminal immunotherapies which apply (genetically-modified) macrophages in a plethora of disease entities such as cirrhosis, infections, chronic inflammation or cancer are currently explored. To meet the growing demand of therapeutically active macrophages for cell-based immunotherapies, the robust production and tailored design of specific macrophage subsets from human induced pluripotent stem cells (iPSC) represents a promising strategy. Here, we demonstrate the continuous production of standardized, highly pure CD45+CD11b+CD14+CD163+ iPSC-derived macrophages (iMonoMac) in scalable quantities using industry compatible bioreactors. To tailor the iMonoMac cell product further to the therapeutic application, we first enhanced the anti-microbial function of macrophages, by pre-loading of the cells with the antibiotics Gentamicin and Levofloxacin. Interestingly, Gentamicin remained intracellular in the iMonoMac for >24 hours, hinting to a direct role in the enhanced intracellular killing. In contrast, Levofloxacin was released from iMonoMac into the medium, suggesting a possibility to utilize preloaded iMonoMac as a carrier to deliver drugs to the site of infection in addition to the intrinsic antimicrobial potential of the cell. Next, we utilized polarization with different cytokines to imprint pro- or anti-inflammatory phenotypes in the iMonoMac, as demonstrated by changes in surface marker profile, cytokine secretion or gene expression. Of note, these M1- or M2-iMonoMac maintain key characteristics of their activation profile upon a secondary inflammatory stimulus. We here provide the tailored design of iMonoMac, which can be used for various cell-based immunotherapies and future applications in the field of regenerative medicine.

Sekretariat der DG-GT e.V.
Institut für Experimentelle Hämatologie
Hildegard Büning
Carl-Neuberg-Str. 1
30625 Hannover

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© 2021 Die Deutsche Gesellschaft für Gentherapie e.V.

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