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

Jamie I. Scott, Sara Gutkin, Ori Green, Emily J. Thompson, Takanori Kitamura, Doron Shabat, Marc Vendrell

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)5699-5703
Number of pages5
JournalAngewandte Chemie - International Edition
Volume60
Issue number11
DOIs
StatePublished - 8 Mar 2021

Keywords

  • activatable probes
  • cancer
  • chemiluminescence
  • immunology
  • natural killer cells

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