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

• Published in: Nature communications 2018-03, Vol.9 (1), p.1081-12, Article 1081
• Main Authors: Emami-Shahri, Nia, Foster, Julie, Kashani, Roxana, Gazinska, Patrycja, Cook, Celia, Sosabowski, Jane, Maher, John, Papa, Sophie
• Format: Article
• Language: English
• Subjects: 13/107; 13/31; 13/44; 14; 42/109; 59; 59/5; 59/78; 631/67/1059/2325; 631/67/2321; 64/60; 96/106; Animals; Antigens; Antigens, CD19 - genetics; Antigens, CD19 - metabolism; B-Lymphocytes - immunology; B-Lymphocytes - metabolism; Biocompatibility; Cancer; CD19 antigen; Cell Line; Chimeric antigen receptors; Flow Cytometry; Hematology; Humanities and Social Sciences; Humans; Image resolution; Immunogenicity; Immunotherapy; Iodides; Lymphocytes; Lymphocytes B; Lymphocytes T; Male; Malignancy; Mice; Mice, SCID; multidisciplinary; Receptors, Antigen, T-Cell - genetics; Receptors, Antigen, T-Cell - metabolism; Science; Science (multidisciplinary); Sodium; Sodium iodide; Sodium iodide symporter; Solid tumors; Spatial distribution; Symporters - genetics; Symporters - metabolism; T cell receptors; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Toxicity; Tumors
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-018-03524-1

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. Adoptive transfer of chimeric antigen receptor (CAR) T cells has shown promising anticancer results in clinical trials. Here the authors use the human sodium iodide symporter (hNIS) as a reporter gene to image human CAR T cells in cancer-bearing mice using broadly available tracers and imaging platforms.