Preprint Article Version 1 This version is not peer-reviewed

Digital Magnetic Sorting for Fractionating Cell Populations with Variable Antigen Expression in Cell Therapy Process Development

Version 1 : Received: 13 September 2024 / Approved: 15 September 2024 / Online: 16 September 2024 (09:54:30 CEST)

How to cite: Bshara-Corson, S.; Burwell, A.; Tiemann, T.; Murray, C. Digital Magnetic Sorting for Fractionating Cell Populations with Variable Antigen Expression in Cell Therapy Process Development. Preprints 2024, 2024091162. https://doi.org/10.20944/preprints202409.1162.v1 Bshara-Corson, S.; Burwell, A.; Tiemann, T.; Murray, C. Digital Magnetic Sorting for Fractionating Cell Populations with Variable Antigen Expression in Cell Therapy Process Development. Preprints 2024, 2024091162. https://doi.org/10.20944/preprints202409.1162.v1

Abstract

Cellular therapies exhibit immense potential in treating complex diseases with sustained response. Manufacture of cell therapies involves purification and engineering of specific cells from a donor or patient to achieve a therapeutic response upon injection. Magnetic cell sorting targeting the presence or absence of surface markers is commonly used for upfront purification. However, emerging research is showing that optimal therapeutic phenotypes are characterized not only by the presence or absence of specific antigens but also on antigen density. Unfortunately, current cell purification tools like magnetic or fluorescence activated cell sorting lack the resolution to differentiate populations based on antigen density while maintaining scalability. Utilizing a technique known as Digital Magnetic Sorting (DMS) we demonstrate proof of concept for a scalable, magnetic based approach to fractionate cell populations based on antigen density level. Targeting CD4 on human leukocytes, DMS demonstrated fractionation into CD4High T cells and CD4Low monocytes/neutrophils as quantified by flow cytometry and single cell RNA sequencing. DMS also demonstrated high throughput processing at throughputs 5-10X faster than flow cytometry. We believe DMS can be leveraged and scaled to enable antigen density-based sorting in cell therapy manufacturing, leading to the production of more potent and sustainable cellular therapies.

Keywords

Cell Therapy Manufacturing; Digital Magnetic Sorting; Antigen Density

Subject

Biology and Life Sciences, Life Sciences

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