Antigen-Dependent Inducible T-Cell Reporter System for PET Imaging of Breast Cancer and Glioblastoma
| العنوان: | Antigen-Dependent Inducible T-Cell Reporter System for PET Imaging of Breast Cancer and Glioblastoma |
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| المؤلفون: | Jaehoon Shin, Matthew F. L. Parker, Iowis Zhu, Aryn Alanizi, Carlos I. Rodriguez, Raymond Liu, Payal B. Watchmaker, Mausam Kalita, Joseph Blecha, Justin Luu, Brian Wright, Suzanne E. Lapi, Robert R. Flavell, Hideho Okada, Thea D. Tlsty, Kole T. Roybal, David M. Wilson |
| المصدر: | Journal of nuclear medicine : official publication, Society of Nuclear Medicine, vol 64, iss 1 |
| بيانات النشر: | Society of Nuclear Medicine, 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | CAR T, SNIPR, T-Lymphocytes, cancer antigens, Clinical Sciences, Breast Neoplasms, Cell Line, Breast Cancer, Genetics, reporter, Animals, Humans, Radiology, Nuclear Medicine and imaging, Cancer, Tumor, 5.2 Cellular and gene therapies, Neurosciences, Nuclear Medicine & Medical Imaging, PET, Genes, Positron-Emission Tomography, Biomedical Imaging, Female, Development of treatments and therapeutic interventions, Glioblastoma, Biotechnology |
| الوصف: | For the past several decades, chimeric antigen receptor T cell (CAR T) therapies have shown promise in the treatment of cancers. These treatments would greatly benefit from companion imaging biomarkers to follow the trafficking of T cells in vivo. Using synthetic biology, we engineered T cells with a chimeric receptor SyNthetic Intramembrane Proteolysis Receptor (SNIPR) that induces overexpression of an exogenous reporter gene cassette upon recognition of specific tumor markers. We then applied a SNIPR-based positron emission tomography (PET) reporter system to two cancer-relevant antigens, human epidermal growth factor receptor 2 (HER2) and epidermal growth factor receptor variant III (EGFRvIII), commonly expressed in breast and glial tumors respectively. Antigen-specific reporter induction of the SNIPR-PET T cells was confirmed in vitro using GFP fluorescence, luciferase luminescence, and the HSV-TK PET reporter with [18F]FHBG. T cells associated with their target antigens were successfully imaged using PET in dual xenograft HER2+/HER2- and EGFRvIII+/EGFRvIII-animal models, with > 10-fold higher [18F]FHBG signals seen in antigen-expressing tumors versus the corresponding controls. The main innovation described is therefore PET detection of T cells via specific antigen-induced signals, in contrast to reporter systems relying on constitutive gene expression. |
| وصف الملف: | application/pdf |
| تدمد: | 2159-662X 0161-5505 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::802e364c992d32156f510ca36ba5715aTest https://doi.org/10.2967/jnumed.122.264284Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....802e364c992d32156f510ca36ba5715a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 2159662X 01615505 |
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