2. Academic Validation
  3. A Functional Chemiluminescent Probe for in Vivo Imaging of Natural Killer Cell Activity Against Tumours

A Functional Chemiluminescent Probe for in Vivo Imaging of Natural Killer Cell Activity Against Tumours

  • Angew Chem Int Ed Engl. 2021 Mar 8;60(11):5699-5703. doi: 10.1002/anie.202011429.
Jamie I Scott 1,  Sara Gutkin 2,  Ori Green 2,  Emily J Thompson 1,  Takanori Kitamura 3,  Doron Shabat 2,  Marc Vendrell 1
Affiliations

Affiliations

  • 1 Centre for Inflammation Research, The University of Edinburgh, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK.
  • 2 Tel Aviv University, Dpt of Organic Chemistry, School of Chemistry, Faculty of Exact Sciences, Tel Aviv, 69978, Israel.
  • 3 MRC Centre for Reproductive Health, The University of Edinburgh, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK.
PMID: 33300671 DOI: 10.1002/anie.202011429
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.

Keywords

activatable probes; cancer; chemiluminescence; immunology; natural killer cells.

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