期刊
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
卷 60, 期 11, 页码 5699-5703出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.202011429
关键词
activatable probes; cancer; chemiluminescence; immunology; natural killer cells
资金
- EPSRC
- MRC Centre for Doctoral Training in Optical Medical Imaging OPTIMA [EP/L016559/1]
- Scottish Funding Council [H14052]
- MRC Career Development Award [MR/S006982/1]
- MRC Centre Grant [MR/N022556/1]
- Israel Science Foundation (ISF)
- ERC Consolidator Grant [771443]
- MRC [MR/S006982/1, MR/N022556/1] Funding Source: UKRI
A new chemiluminescent probe has been developed to image the killing activity of NK cells against cancer cells in vivo, demonstrating high selectivity and signal-to-noise ratios. This is the first chemiluminescent probe for in vivo imaging of NK cell activity in live tumors.
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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