Engineered immune cells as highly sensitive cancer diagnostics

Nat Biotechnol. 2019 May;37(5):531-539. doi: 10.1038/s41587-019-0064-8. Epub 2019 Mar 18.

Abstract

Endogenous biomarkers remain at the forefront of early disease detection efforts, but many lack the sensitivities and specificities necessary to influence disease management. Here, we describe a cell-based in vivo sensor for highly sensitive early cancer detection. We engineer macrophages to produce a synthetic reporter on adopting an M2 tumor-associated metabolic profile by coupling luciferase expression to activation of the arginase-1 promoter. After adoptive transfer in colorectal and breast mouse tumor models, the engineered macrophages migrated to the tumors and activated arginase-1 so that they could be detected by bioluminescence imaging and luciferase measured in the blood. The macrophage sensor detected tumors as small as 25-50 mm3 by blood luciferase measurements, even in the presence of concomitant inflammation, and was more sensitive than clinically used protein and nucleic acid cancer biomarkers. Macrophage sensors also effectively tracked the immunological response in muscle and lung models of inflammation, suggesting the potential utility of this approach in disease states other than cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arginase / blood*
  • Arginase / genetics
  • Arginase / immunology
  • Biomarkers, Tumor / blood
  • Cell Engineering
  • Disease Models, Animal
  • Early Detection of Cancer*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Luciferases / blood
  • Luciferases / genetics
  • Luciferases / immunology
  • Macrophages / immunology*
  • Mice
  • Neoplasms / blood*
  • Neoplasms / immunology
  • Neoplasms / pathology

Substances

  • Biomarkers, Tumor
  • Luciferases
  • Arginase
  • arginase I, human