研究动态
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对过继转移的 T 细胞进行高效磁泳标记,用于纵向体内磁粒子成像。

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

发表日期:2024
作者: Rong En Tay, Lokamitra P, Shun Toll Pang, Kay En Low, Hui Chien Tay, Charmaine Min Ho, Benoit Malleret, Olaf Rötzschke, Malini Olivo, Zhi Wei Tay
来源: Theranostics

摘要:

虽然过继细胞疗法(ACT)作为血癌疗法取得了成功,但它们在治疗实体瘤方面的功效有限,因为肿瘤微环境排除并抑制过继转移的肿瘤特异性免疫细胞。改善实体瘤细胞疗法的一个主要障碍是缺乏能够在体内长时间跟踪 ACT 产品的迁移和免疫功能活性的可用和定量成像方式。方法:开发了一种高效磁泳方法,可以轻松地对难以标记的免疫细胞进行磁性标记,然后将其注射到荷瘤小鼠体内,并使用紧凑型台式磁粒子成像仪(MPI)设计在两周内进行成像。结果:标记效率比之前的研究提高了 10 倍以上,能够在体内对标记的免疫细胞及其相对于肿瘤的生物分布进行至少两周的长期跟踪。新成像仪的吞吐量提高了 5 倍,可实现更大的数据密度(每个实验最多 20 只小鼠)。结论:总而言之,我们的创新使得 MPI 能够方便实用地使用,以可视化 ACT 产品在体内临床前模型中的定位,从而对治疗效果进行纵向、非侵入性功能评估。© 作者。
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.© The author(s).