Premium
A Functional Chemiluminescent Probe for in Vivo Imaging of Natural Killer Cell Activity Against Tumours
Author(s) -
Scott Jamie I.,
Gutkin Sara,
Green Ori,
Thompson Emily J.,
Kitamura Takanori,
Shabat Doron,
Vendrell Marc
Publication year - 2021
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.202011429
Subject(s) - granzyme b , granzyme , in vivo , chemiluminescence , natural killer cell , chemistry , cancer cell , cell , cancer research , in vitro , biology , cytotoxicity , perforin , cancer , biochemistry , genetics , microbiology and biotechnology , organic chemistry
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.