Emami-Shahri Nia, Foster Julie, Kashani Roxana, Gazinska Patrycja, Cook Celia, Sosabowski Jane, Maher John, Papa Sophie
ImmunoEngineering Group, King's College London, Division of Cancer Studies, 3rd Floor Bermondsey Wing, King's Health Partners Integrated Cancer Centre, Great Maze Pond, Guy's Hospital, London, SE1 9RT, UK.
Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, London, EC1M 6BQ, UK.
Nat Commun. 2018 Mar 14;9(1):1081. doi: 10.1038/s41467-018-03524-1.
The unprecedented efficacy of chimeric antigen receptor (CAR) T-cell immunotherapy of CD19 B-cell malignancy has established a new therapeutic pillar of hematology-oncology. Nonetheless, formidable challenges remain for the attainment of comparable success in patients with solid tumors. To accelerate progress and rapidly characterize emerging toxicities, systems that permit the repeated and non-invasive assessment of CAR T-cell bio-distribution would be invaluable. An ideal solution would entail the use of a non-immunogenic reporter that mediates specific uptake of an inexpensive, non-toxic and clinically established imaging tracer by CAR T cells. Here we show the utility of the human sodium iodide symporter (hNIS) for the temporal and spatial monitoring of CAR T-cell behavior in a cancer-bearing host. This system provides a clinically compliant toolkit for high-resolution serial imaging of CAR T cells in vivo, addressing a fundamental unmet need for future clinical development in the field.
嵌合抗原受体（CAR）T细胞免疫疗法对CD19 B细胞恶性肿瘤具有前所未有的疗效，为血液肿瘤学建立了新的治疗支柱。尽管如此，在实体瘤患者中取得类似的成功仍面临巨大挑战。为了加速进展并快速表征新出现的毒性，能够对CAR T细胞生物分布进行重复和非侵入性评估的系统将非常宝贵。一个理想的解决方案是使用一种非免疫原性报告基因，该基因介导CAR T细胞对一种廉价、无毒且临床已确立的成像示踪剂的特异性摄取。在这里，我们展示了人类钠碘同向转运体（hNIS）在荷瘤宿主中对CAR T细胞行为进行时空监测的效用。该系统为体内CAR T细胞的高分辨率连续成像提供了一个符合临床要求的工具包，满足了该领域未来临床发展中一个尚未得到满足的基本需求。
