Enrichment of T-lymphocytes from leukemic blood using inertial microfluidics toward improved chimeric antigen receptor-T cell manufacturing.

Elsemary, MT; Maritz, MF; Smith, LE; Warkiani, ME; Thierry, B

Enrichment of T-lymphocytes from leukemic blood using inertial microfluidics toward improved chimeric antigen receptor-T cell manufacturing.

Elsemary, MT Maritz, MF Smith, LE Warkiani, ME Thierry, B

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Publisher:: ELSEVIER SCI LTD
Publication Type:: Journal Article
Citation:: Cytotherapy, 2024, 26, (10), pp. 1264-1274
Issue Date:: 2024-10

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Field	Value	Language
dc.contributor.author	Elsemary, MT
dc.contributor.author	Maritz, MF
dc.contributor.author	Smith, LE
dc.contributor.author	Warkiani, ME
dc.contributor.author	Thierry, B
dc.date.accessioned	2025-04-24T03:52:46Z
dc.date.available	2024-05-05
dc.date.available	2025-04-24T03:52:46Z
dc.date.issued	2024-10
dc.identifier.citation	Cytotherapy, 2024, 26, (10), pp. 1264-1274
dc.identifier.issn	1465-3249
dc.identifier.issn	1477-2566
dc.identifier.uri	http://hdl.handle.net/10453/187021
dc.description.abstract	Chimeric antigen receptor cell therapy is a successful immunotherapy for the treatment of blood cancers. However, hurdles in their manufacturing remain including efficient isolation and purification of the T-cell starting material. Herein, we describe a one-step separation based on inertial spiral microfluidics for efficient enrichment of T-cells in B-cell acute lymphoblastic leukemia (ALL) and B-cell chronic lymphocytic leukemia patient's samples. In healthy donors used to optimize the process, the lymphocyte purity was enriched from 65% (SD ± 0.2) to 91% (SD ± 0.06) and T-cell purity was enriched from 45% (SD ± 0.1) to 73% (SD ± 0.02). Leukemic samples had higher starting B-cells compared to the healthy donor samples. Efficient enrichment and recovery of lymphocytes and T-cells were achieved in ALL samples with B-cells, monocytes and leukemic blasts depleted by 80% (SD ± 0.09), 89% (SD ± 0.1) and 74% (SD ± 0.09), respectively, and a 70% (SD ± 0.1) T-cell recovery. Chronic lymphocytic leukemia samples had lower T-cell numbers, and the separation process was less efficient compared to the ALL. This study demonstrates the use of inertial microfluidics for T-cell enrichment and depletion of B-cell blasts in ALL, suggesting its potential to address a key bottleneck of the chimeric antigen receptor-T manufacturing workflow.
dc.format	Print-Electronic
dc.language	eng
dc.publisher	ELSEVIER SCI LTD
dc.relation.ispartof	Cytotherapy
dc.relation.isbasedon	10.1016/j.jcyt.2024.05.005
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	1103 Clinical Sciences
dc.subject.classification	Immunology
dc.subject.classification	3204 Immunology
dc.subject.classification	3206 Medical biotechnology
dc.subject.mesh	Humans
dc.subject.mesh	T-Lymphocytes
dc.subject.mesh	Receptors, Chimeric Antigen
dc.subject.mesh	Immunotherapy, Adoptive
dc.subject.mesh	Microfluidics
dc.subject.mesh	Leukemia, Lymphocytic, Chronic, B-Cell
dc.subject.mesh	Cell Separation
dc.subject.mesh	B-Lymphocytes
dc.subject.mesh	Precursor Cell Lymphoblastic Leukemia-Lymphoma
dc.subject.mesh	Receptors, Antigen, T-Cell
dc.subject.mesh	B-Lymphocytes
dc.subject.mesh	T-Lymphocytes
dc.subject.mesh	Humans
dc.subject.mesh	Receptors, Antigen, T-Cell
dc.subject.mesh	Immunotherapy, Adoptive
dc.subject.mesh	Cell Separation
dc.subject.mesh	Microfluidics
dc.subject.mesh	Leukemia, Lymphocytic, Chronic, B-Cell
dc.subject.mesh	Precursor Cell Lymphoblastic Leukemia-Lymphoma
dc.subject.mesh	Receptors, Chimeric Antigen
dc.subject.mesh	Humans
dc.subject.mesh	T-Lymphocytes
dc.subject.mesh	Receptors, Chimeric Antigen
dc.subject.mesh	Immunotherapy, Adoptive
dc.subject.mesh	Microfluidics
dc.subject.mesh	Leukemia, Lymphocytic, Chronic, B-Cell
dc.subject.mesh	Cell Separation
dc.subject.mesh	B-Lymphocytes
dc.subject.mesh	Precursor Cell Lymphoblastic Leukemia-Lymphoma
dc.subject.mesh	Receptors, Antigen, T-Cell
dc.title	Enrichment of T-lymphocytes from leukemic blood using inertial microfluidics toward improved chimeric antigen receptor-T cell manufacturing.
dc.type	Journal Article
utslib.citation.volume	26
utslib.location.activity	England
utslib.for	1103 Clinical Sciences
pubs.organisational-group	University of Technology Sydney
pubs.organisational-group	University of Technology Sydney/Faculty of Engineering and Information Technology
pubs.organisational-group	University of Technology Sydney/Faculty of Engineering and Information Technology/School of Biomedical Engineering
pubs.organisational-group	University of Technology Sydney/UTS Groups
pubs.organisational-group	University of Technology Sydney/UTS Groups/Centre for Health Technologies (CHT)
pubs.organisational-group	University of Technology Sydney/UTS Groups/Institute of Biomedical Materials and Devices (IBMD)
pubs.organisational-group	University of Technology Sydney/UTS Groups/Institute of Biomedical Materials and Devices (IBMD)/Institute of Biomedical Materials and Devices (IBMD) Associate Members
utslib.copyright.status	open_access	*
dc.rights.license	This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0). To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/
dc.date.updated	2025-04-24T03:52:43Z
pubs.issue	10
pubs.publication-status	Published
pubs.volume	26
utslib.citation.issue	10

Abstract:

Chimeric antigen receptor cell therapy is a successful immunotherapy for the treatment of blood cancers. However, hurdles in their manufacturing remain including efficient isolation and purification of the T-cell starting material. Herein, we describe a one-step separation based on inertial spiral microfluidics for efficient enrichment of T-cells in B-cell acute lymphoblastic leukemia (ALL) and B-cell chronic lymphocytic leukemia patient's samples. In healthy donors used to optimize the process, the lymphocyte purity was enriched from 65% (SD ± 0.2) to 91% (SD ± 0.06) and T-cell purity was enriched from 45% (SD ± 0.1) to 73% (SD ± 0.02). Leukemic samples had higher starting B-cells compared to the healthy donor samples. Efficient enrichment and recovery of lymphocytes and T-cells were achieved in ALL samples with B-cells, monocytes and leukemic blasts depleted by 80% (SD ± 0.09), 89% (SD ± 0.1) and 74% (SD ± 0.09), respectively, and a 70% (SD ± 0.1) T-cell recovery. Chronic lymphocytic leukemia samples had lower T-cell numbers, and the separation process was less efficient compared to the ALL. This study demonstrates the use of inertial microfluidics for T-cell enrichment and depletion of B-cell blasts in ALL, suggesting its potential to address a key bottleneck of the chimeric antigen receptor-T manufacturing workflow.

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http://hdl.handle.net/10453/187021