High-efficiency magnetophoretic labelling of adoptively- transferred T cells for longitudinal in vivo Magnetic Particle

被引:2
作者
Tay, Rong En [1 ,9 ]
Lokamitra, P. [1 ,2 ]
Pang, Shun Toll [2 ,8 ]
Low, Kay En [3 ]
Tay, Hui Chien [1 ]
Ho, Charmaine Min [1 ]
Malleret, Benoit [3 ,4 ]
Roetzschke, Olaf [4 ,5 ]
Olivo, Malini [6 ]
Tay, Zhi Wei [2 ,7 ]
机构
[1] ASTAR, Singapore Immunol Network SIgN, 8A Biomed Grove,04-06 Immunos, Singapore 138648, Singapore
[2] ASTAR, Inst Bioengn & Bioimaging IBB, 11 Biopolis Way,02-02 Helios Bldg, Singapore 138667, Singapore
[3] Natl Univ Singapore, Yong Loo Lin Sch Med, Electron Microscopy Unit, Singapore 117597, Singapore
[4] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Microbiol & Immunol, Immunol Translat Res Programme, Singapore, Singapore
[5] Nanyang Technol Univ, Sch Biol Sci, 50 Nanyang Ave, Singapore 639798, Singapore
[6] ASTAR, ASTAR Skin Res Labs ASRL, 31 Biopolis Way,07-01 Nanos, Singapore 138669, Singapore
[7] Natl Inst Adv Ind Sci & Technol, Hlth & Med Res Inst HMRI, 1-2-1 Namiki, Tsukuba, Ibaraki 3058564, Japan
[8] Inst Tech Educ, 2 Ang Mo Kio Dr, Singapore 567720, Singapore
[9] Natl Inst Adv Ind Sci & Technol, Hlth & Med Res Inst HMRI, Adv Mfg Res Inst, 1-2-1 Namiki, Tsukuba, Ibaraki 3058564, Japan
基金
英国医学研究理事会;
关键词
TRACKING; NANOPARTICLE; BIODISTRIBUTION; SENSITIVITY; CLEARANCE; SAFETY; AGENTS; LIVER;
D O I
10.7150/thno.95527
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
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.
引用
收藏
页码:6138 / 6160
页数:23
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