Format

Send to

Choose Destination
JCI Insight. 2016 Nov 17;1(19):e90064.

Longitudinal PET imaging demonstrates biphasic CAR T cell responses in survivors.

Author information

1
Molecular Imaging Innovations Institute, Department of Radiology, Weill Cornell Medicine, New York, New York, USA.; Department of Biomedical Engineering, Cornell University, Ithaca, New York, USA.
2
Molecular Imaging Innovations Institute, Department of Radiology, Weill Cornell Medicine, New York, New York, USA.
3
Department of Surgery, Weill Cornell Medicine, New York, New York, USA.
4
Molecular Imaging Innovations Institute, Department of Radiology, Weill Cornell Medicine, New York, New York, USA.; Department of Pathology, Chonnam National University Medical School, Gwangju, South Korea.
5
Molecular Imaging Innovations Institute, Department of Radiology, Weill Cornell Medicine, New York, New York, USA.; Department of Biomedical Engineering, Cornell University, Ithaca, New York, USA.; Department of Surgery, Weill Cornell Medicine, New York, New York, USA.

Abstract

Clinical monitoring of adoptive T cell transfer (ACT) utilizes serial blood analyses to discern T cell activity. While useful, these data are 1-dimensional and lack spatiotemporal information related to treatment efficacy or toxicity. We utilized a human genetic reporter, somatostatin receptor 2 (SSTR2), and PET, to quantitatively and longitudinally visualize whole-body T cell distribution and antitumor dynamics using a clinically approved radiotracer. Initial evaluations determined that SSTR2-expressing T cells were detectable at low densities with high sensitivity and specificity. SSTR2-based PET was applied to ACT of chimeric antigen receptor (CAR) T cells targeting intercellular adhesion molecule-1, which is overexpressed in anaplastic thyroid tumors. Timely CAR T cell infusions resulted in survival of tumor-bearing mice, while later infusions led to uniform death. Real-time PET imaging revealed biphasic T cell expansion and contraction at tumor sites among survivors, with peak tumor burden preceding peak T cell burden by several days. In contrast, nonsurvivors displayed unrelenting increases in tumor and T cell burden, indicating that tumor growth was outpacing T cell killing. Thus, longitudinal PET imaging of SSTR2-positive ACT dynamics enables prognostic, spatiotemporal monitoring with unprecedented clarity and detail to facilitate comprehensive therapy evaluation with potential for clinical translation.

PMID:
27882353
PMCID:
PMC5111513
DOI:
10.1172/jci.insight.90064
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for American Society for Clinical Investigation Icon for PubMed Central
Loading ...
Support Center