High-efficiency magnetophoretic labelling of adoptively-transferred T cells for longitudinal in vivo magnetic particle imaging
While adoptive cell therapies (ACT) have been successful as therapies for blood cancers, they have limited efficacy in treating solid tumours, where the tumour microenvironment excludes and suppresses adoptively transferred tumour-specific immune cells. A major obstacle to improving cell therapies f...
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sg-ntu-dr.10356-1817372024-12-16T15:32:31Z High-efficiency magnetophoretic labelling of adoptively-transferred T cells for longitudinal in vivo magnetic particle imaging Tay, Rong En Lokamitra, P. Pang, Shun Toll Low, Kay En Tay, Hui Chien Ho, Charmaine Min Malleret, Benoit Rötzschke, Olaf Olivo, Malini Tay, Zhi Wei School of Biological Sciences Singapore Immunology Network, A*STAR Yong Loo Lin School of Medicine, NUS Medicine, Health and Life Sciences High efficiency magnetophoretic labelling High throughput imaging While adoptive cell therapies (ACT) have been successful as therapies for blood cancers, they have limited efficacy in treating solid tumours, where the tumour microenvironment excludes and suppresses adoptively transferred tumour-specific immune cells. A major obstacle to improving cell therapies for solid tumours is a lack of accessible and quantitative imaging modalities capable of tracking the migration and immune functional activity of ACT products for an extended duration in vivo. Methods: A high-efficiency magnetophoretic method was developed for facile magnetic labelling of hard-to-label immune cells, which were then injected into tumour-bearing mice and imaged over two weeks with a compact benchtop Magnetic Particle Imager (MPI) design. Results: Labelling efficiency was improved more than 10-fold over prior studies enabling longer-term tracking for at least two weeks in vivo of the labelled immune cells and their biodistribution relative to the tumour. The new imager showed 5-fold improved throughput enabling much larger density of data (up to 20 mice per experiment). Conclusions: Taken together, our innovations enable the convenient and practical use of MPI to visualise the localisation of ACT products in in vivo preclinical models for longitudinal, non-invasive functional evaluation of therapeutic efficacy. Agency for Science, Technology and Research (A*STAR) Published version This research is supported by funding from A*STAR Career Development Award #202D800036, and core funding from the Singapore Immunology Network (SIgN) and the Institute for Bioengineering and Bioimaging (IBB), Agency for Science, Technology and Research (A*STAR). R.E.T. and C.M.H. gratefully acknowledge additional support from an Open Fund-Young Individual Research Grant (OFYIRG21jun-0052) from the Singapore National Medical Research Council and a Pre-Pilot Award (H23G1a0005) from the Singapore Therapeutics Development Review. Z.W.T and M.O. gratefully acknowledges the additional funding support from the Agency of Science Technology and Research’s (A*STAR) BMRC Central Research Fund (CRF, UIBR) Award. 2024-12-16T06:42:22Z 2024-12-16T06:42:22Z 2024 Journal Article Tay, R. E., Lokamitra, P., Pang, S. T., Low, K. E., Tay, H. C., Ho, C. M., Malleret, B., Rötzschke, O., Olivo, M. & Tay, Z. W. (2024). High-efficiency magnetophoretic labelling of adoptively-transferred T cells for longitudinal in vivo magnetic particle imaging. Theranostics, 14(16), 6138-6160. https://dx.doi.org/10.7150/thno.95527 1838-7640 https://hdl.handle.net/10356/181737 10.7150/thno.95527 39431019 2-s2.0-85204996890 16 14 6138 6160 en 202D800036 Theranostics © The author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions. application/pdf |
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Medicine, Health and Life Sciences High efficiency magnetophoretic labelling High throughput imaging Tay, Rong En Lokamitra, P. Pang, Shun Toll Low, Kay En Tay, Hui Chien Ho, Charmaine Min Malleret, Benoit Rötzschke, Olaf Olivo, Malini Tay, Zhi Wei High-efficiency magnetophoretic labelling of adoptively-transferred T cells for longitudinal in vivo magnetic particle imaging |
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While adoptive cell therapies (ACT) have been successful as therapies for blood cancers, they have limited efficacy in treating solid tumours, where the tumour microenvironment excludes and suppresses adoptively transferred tumour-specific immune cells. A major obstacle to improving cell therapies for solid tumours is a lack of accessible and quantitative imaging modalities capable of tracking the migration and immune functional activity of ACT products for an extended duration in vivo. Methods: A high-efficiency magnetophoretic method was developed for facile magnetic labelling of hard-to-label immune cells, which were then injected into tumour-bearing mice and imaged over two weeks with a compact benchtop Magnetic Particle Imager (MPI) design. Results: Labelling efficiency was improved more than 10-fold over prior studies enabling longer-term tracking for at least two weeks in vivo of the labelled immune cells and their biodistribution relative to the tumour. The new imager showed 5-fold improved throughput enabling much larger density of data (up to 20 mice per experiment). Conclusions: Taken together, our innovations enable the convenient and practical use of MPI to visualise the localisation of ACT products in in vivo preclinical models for longitudinal, non-invasive functional evaluation of therapeutic efficacy. |
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School of Biological Sciences |
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School of Biological Sciences Tay, Rong En Lokamitra, P. Pang, Shun Toll Low, Kay En Tay, Hui Chien Ho, Charmaine Min Malleret, Benoit Rötzschke, Olaf Olivo, Malini Tay, Zhi Wei |
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Article |
author |
Tay, Rong En Lokamitra, P. Pang, Shun Toll Low, Kay En Tay, Hui Chien Ho, Charmaine Min Malleret, Benoit Rötzschke, Olaf Olivo, Malini Tay, Zhi Wei |
author_sort |
Tay, Rong En |
title |
High-efficiency magnetophoretic labelling of adoptively-transferred T cells for longitudinal in vivo magnetic particle imaging |
title_short |
High-efficiency magnetophoretic labelling of adoptively-transferred T cells for longitudinal in vivo magnetic particle imaging |
title_full |
High-efficiency magnetophoretic labelling of adoptively-transferred T cells for longitudinal in vivo magnetic particle imaging |
title_fullStr |
High-efficiency magnetophoretic labelling of adoptively-transferred T cells for longitudinal in vivo magnetic particle imaging |
title_full_unstemmed |
High-efficiency magnetophoretic labelling of adoptively-transferred T cells for longitudinal in vivo magnetic particle imaging |
title_sort |
high-efficiency magnetophoretic labelling of adoptively-transferred t cells for longitudinal in vivo magnetic particle imaging |
publishDate |
2024 |
url |
https://hdl.handle.net/10356/181737 |
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1819113075818627072 |