Antigen-Dependent Inducible T-Cell Reporter System for PET Imaging of Breast Cancer and Glioblastoma
| Autor: | 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 |
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| Rok vydání: | 2022 |
| Předmět: |
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 |
| Zdroj: | Journal of nuclear medicine : official publication, Society of Nuclear Medicine, vol 64, iss 1 |
| ISSN: | 2159-662X 0161-5505 |
| DOI: | 10.2967/jnumed.122.264284 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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