Longitudinal PET imaging demonstrates biphasic CAR T cell responses in survivors
| Autor: | Marjan Zaman, Richard Ting, Enda Shevlin, Benedict Law, Young Tai Kim, Susan Park, Yogindra Vedvyas, Moonsoo M. Jin, Yonghua Luo, Alejandro Amor-Coarasa, Keon-Woo Kwon, Do Hyun Kim, Irene M. Min, John W. Babich, Spencer Park, Turner Smith |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Cytotoxicity Immunologic Pathology medicine.medical_specialty T cell medicine.medical_treatment T-Lymphocytes Receptors Antigen T-Cell Jurkat cells Immunotherapy Adoptive Cell Line 03 medical and health sciences Jurkat Cells Mice 0302 clinical medicine Antigen Genes Reporter Transduction Genetic Cell Line Tumor medicine Somatostatin receptor 2 Animals Humans Receptor business.industry General Medicine Immunotherapy Neoplasms Experimental Xenograft Model Antitumor Assays Chimeric antigen receptor 3. Good health 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Positron-Emission Tomography Cancer research business Intracellular Research Article |
| Zdroj: | JCI insight. 1(19) |
| ISSN: | 2379-3708 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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