化学发光
体内
化学
自然杀伤细胞
颗粒酶B
颗粒酶
癌细胞
细胞
过继性细胞移植
癌症研究
体外
细胞毒性T细胞
生物化学
细胞毒性
癌症
生物
有机化学
生物技术
穿孔素
遗传学
作者
Jamie I. Scott,Sara Gutkin,Ori Green,Emily Thompson,Takanori Kitamura,Doron Shabat,Marc Vendrell
标识
DOI:10.1002/anie.202011429
摘要
Abstract Natural killer (NK) cells are immune cells that can kill certain types of cancer cells. Adoptive transfer of NK cells represents a promising immunotherapy for malignant tumours; however, there is a lack of methods to validate anti‐tumour activity of NK cells in vivo. Herein, we report a new chemiluminescent probe to image in situ the granzyme B‐mediated killing activity of NK cells against cancer cells. We have optimised a granzyme B‐specific construct using an activatable phenoxydioxetane reporter so that enzymatic cleavage of the probe results in bright chemiluminescence. The probe shows high selectivity for active granzyme B over other proteases and higher signal‐to‐noise ratios than commercial fluorophores. Finally, we demonstrate that the probe can detect NK cell activity in mouse models, being the first chemiluminescent probe for in vivo imaging of NK cell activity in live tumours.
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