Tay, R. E., P, L., 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://doi.org/10.7150/thno.95527
Abstract:
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.
License type:
Attribution 4.0 International (CC BY 4.0)
Funding Info:
This research / project is supported by the Agency for Science, Technology and Research (A*STAR) - Career Development Fund
Grant Reference no. : 202D800036
This research / project is supported by the National Medical Research Council - Open Fund-Young Individual Research Grant
Grant Reference no. : OFYIRG21jun-0052
This research / project is supported by the Singapore Therapeutics Development Review - Pre-Pilot Award
Grant Reference no. : H23G1a0005
This research / project is supported by the A*STAR Biomedical Research Council - Central Research Fund - Use Inspired Basic Research
Grant Reference no. : Central Research Fund
This research is supported by core funding from: Singapore Immunology Network (SIgN) and the Institute for Bioengineering and Bioimaging (IBB)
Grant Reference no. :