Clinically Compliant Spatial and Temporal Imaging of Chimeric Antigen Receptor T-cells

TY - JOUR

T1 - Clinically Compliant Spatial and Temporal Imaging of Chimeric Antigen Receptor T-cells

AU - Emami-Shahri, Nia

AU - Foster, Julie

AU - Kashani, Roxana

AU - Gazinska, Patrycja

AU - Cook, Celia

AU - Maher, John

AU - Sosabowski, Jane

AU - Papa, Sophie

PY - 2018/3/14

Y1 - 2018/3/14

N2 - 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.

AB - 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.

U2 - 10.1038/s41467-018-03524-1

DO - 10.1038/s41467-018-03524-1

M3 - Article

SN - 2041-1723

VL - 9

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 1081

ER -