Clinically compliant spatial and temporal imaging of chimeric antigen receptor T-cells

Nia Emami-Shahri, Julie Foster, Roxana Kashani, Patrycja Gazinska, Celia Cook, Jane Sosabowski, John Maher and Sophie Papa ()
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Nia Emami-Shahri: King’s Health Partners Integrated Cancer Centre, Great Maze Pond, Guy’s Hospital
Julie Foster: Queen Mary University of London, Charterhouse Square
Roxana Kashani: Queen Mary University of London, Charterhouse Square
Patrycja Gazinska: Guy’s Cancer Centre
Celia Cook: King’s Health Partners Integrated Cancer Centre, Great Maze Pond, Guy’s Hospital
Jane Sosabowski: Queen Mary University of London, Charterhouse Square
John Maher: King’s Health Partners Integrated Cancer Centre, Great Maze Pond, Guy’s Hospital
Sophie Papa: King’s Health Partners Integrated Cancer Centre, Great Maze Pond, Guy’s Hospital

Nature Communications, 2018, vol. 9, issue 1, 1-12

Abstract: Abstract The unprecedented efficacy of chimeric antigen receptor (CAR) T-cell immunotherapy of CD19+ B-cell malignancy has established a new therapeutic pillar of hematology–oncology. Nonetheless, formidable challenges remain for the attainment of comparable success in patients with solid tumors. To accelerate progress and rapidly characterize emerging toxicities, systems that permit the repeated and non-invasive assessment of CAR T-cell bio-distribution would be invaluable. An ideal solution would entail the use of a non-immunogenic reporter that mediates specific uptake of an inexpensive, non-toxic and clinically established imaging tracer by CAR T cells. Here we show the utility of the human sodium iodide symporter (hNIS) for the temporal and spatial monitoring of CAR T-cell behavior in a cancer-bearing host. This system provides a clinically compliant toolkit for high-resolution serial imaging of CAR T cells in vivo, addressing a fundamental unmet need for future clinical development in the field.

Date: 2018
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DOI: 10.1038/s41467-018-03524-1

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