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Longitudinal PET imaging demonstrates biphasic CAR T cell responses in survivors.
Vedvyas, Yogindra; Shevlin, Enda; Zaman, Marjan; Min, Irene M; Amor-Coarasa, Alejandro; Park, Spencer; Park, Susan; Kwon, Keon-Woo; Smith, Turner; Luo, Yonghua; Kim, Dohyun; Kim, Young; Law, Benedict; Ting, Richard; Babich, John; Jin, Moonsoo M.
Afiliación
  • Vedvyas Y; Molecular Imaging Innovations Institute, Department of Radiology, Weill Cornell Medicine, New York, New York, USA.
  • Shevlin E; Department of Biomedical Engineering, Cornell University, Ithaca, New York, USA.
  • Zaman M; Molecular Imaging Innovations Institute, Department of Radiology, Weill Cornell Medicine, New York, New York, USA.
  • Min IM; Molecular Imaging Innovations Institute, Department of Radiology, Weill Cornell Medicine, New York, New York, USA.
  • Amor-Coarasa A; Department of Surgery, Weill Cornell Medicine, New York, New York, USA.
  • Park S; Molecular Imaging Innovations Institute, Department of Radiology, Weill Cornell Medicine, New York, New York, USA.
  • Park S; Molecular Imaging Innovations Institute, Department of Radiology, Weill Cornell Medicine, New York, New York, USA.
  • Kwon KW; Department of Biomedical Engineering, Cornell University, Ithaca, New York, USA.
  • Smith T; Molecular Imaging Innovations Institute, Department of Radiology, Weill Cornell Medicine, New York, New York, USA.
  • Luo Y; Molecular Imaging Innovations Institute, Department of Radiology, Weill Cornell Medicine, New York, New York, USA.
  • Kim D; Molecular Imaging Innovations Institute, Department of Radiology, Weill Cornell Medicine, New York, New York, USA.
  • Kim Y; Molecular Imaging Innovations Institute, Department of Radiology, Weill Cornell Medicine, New York, New York, USA.
  • Law B; Molecular Imaging Innovations Institute, Department of Radiology, Weill Cornell Medicine, New York, New York, USA.
  • Ting R; Molecular Imaging Innovations Institute, Department of Radiology, Weill Cornell Medicine, New York, New York, USA.
  • Babich J; Department of Pathology, Chonnam National University Medical School, Gwangju, South Korea.
  • Jin MM; Molecular Imaging Innovations Institute, Department of Radiology, Weill Cornell Medicine, New York, New York, USA.
JCI Insight ; 1(19): e90064, 2016 11 17.
Article en En | MEDLINE | ID: mdl-27882353
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Receptores de Antígenos de Linfocitos T / Linfocitos T / Inmunoterapia Adoptiva / Tomografía de Emisión de Positrones / Neoplasias Experimentales Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: JCI Insight Año: 2016 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Receptores de Antígenos de Linfocitos T / Linfocitos T / Inmunoterapia Adoptiva / Tomografía de Emisión de Positrones / Neoplasias Experimentales Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: JCI Insight Año: 2016 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos