Non-invasive monitoring of the kinetic infiltration and therapeutic efficacy of nanoparticle-labeled chimeric antigen receptor T cells in glioblastoma via 7.0-Tesla magnetic resonance imaging |
| |
| Authors: | Tian Xie Xiao Chen Jingqin Fang Wei Xue Junfeng Zhang Haipeng Tong Heng Liu Yu Guo Yizeng Yang Weiguo Zhang |
| |
| Institution: | 1. Department of Radiology, Institute of Surgery Research, Daping Hospital, Army Medical University, Chongqing, China;2. Chongqing Clinical Research Center for Imaging and Nuclear Medicine, Chongqing, China;3. Department of Radiology, PLA Rocket Force Characteristic Medical Center, Beijing, China;4. Department of Medicine, Division of Gastroenterology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA;1. Faculty of Health Sciences, Simon Fraser University, Burnaby, Canada;2. Center for Bioethics, University of Minnesota, Minneapolis, Minnesota, USA;1. Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados del IPN, México;2. Departamento de Inmunología Escuela Nacional de Ciencias Biológicas, del Instituto Politécnico Nacional, México;3. Departamento de Matemáticas, Universidad Autónoma Metropolitana-Iztapalapa (UAM-I), México;1. Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA;2. CELLSCRIPT, LLC, Madison, Wisconsin, USA;3. MaxCyte Inc, Gaithersburg, Maryland, USA;4. Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA;5. Molecular Development of the Immune System Section, Laboratory of Immune System Biology and Clinical Genomics Program, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA;1. Department of Diabetes Immunology, Diabetes and Metabolism Research Institute, Beckman Research Institute, City of Hope, Duarte, California, USA;2. Department of Diabetes Complications and Metabolism, Diabetes and Metabolism Research Institute, Beckman Research Institute, City of Hope, Duarte, California, USA;3. Department of Internal Medicine, Leiden University Medical Center, Leiden, the Netherlands;1. University of California San Diego Moores Cancer Center, La Jolla, California, USA;2. PersImmune, Inc, San Diego, California, USA;3. University of California San Diego Apheresis Program and Division of Nephrology, La Jolla, California, USA;1. Immune, Progenitor and Cell Therapeutics Laboratory, Department of Laboratory Medicine and Pathology, Division of Transfusion Medicine, Mayo Clinic, Rochester, Minnesota, USA;2. Department of Laboratory Medicine and Pathology, Division of Clinical Biochemistry and Immunology, Mayo Clinic, Rochester, MN, USA;3. Department of Medicine, Division of Endocrinology, Mayo Clinic, Rochester, MN, USA |
| |
| Abstract: | Background aimsChimeric antigen receptor (CAR) T-cell therapy is a promising treatment strategy in solid tumors. In vivo cell tracking techniques can help us better understand the infiltration, persistence and therapeutic efficacy of CAR T cells. In this field, magnetic resonance imaging (MRI) can achieve high-resolution images of cells by using cellular imaging probes. MRI can also provide various biological information on solid tumors.MethodsThe authors adopted the amino alcohol derivatives of glucose-coated nanoparticles, ultra-small superparamagnetic particles of iron oxide (USPIOs), to label CAR T cells for non-invasive monitoring of kinetic infiltration and persistence in glioblastoma (GBM). The specific targeting CARs included anti-human epidermal growth factor receptor variant III and IL13 receptor subunit alpha 2 CARs.ResultsWhen using an appropriate concentration, USPIO labeling exerted no negative effects on the biological characteristics and killing efficiency of CAR T cells. Increasing hypointensity signals could be detected in GBM models by susceptibility-weighted imaging MRI ranging from 3 days to 14 days following the injection of USPIO-labeled CAR T cells. In addition, nanoparticles and CAR T cells were found on consecutive histopathological sections. Moreover, diffusion and perfusion MRI revealed significantly increased water diffusion and decreased vascular permeability on day 3 after treatment, which was simultaneously accompanied by a significant decrease in tumor cell proliferation and increase in intercellular tight junction on immunostaining sections.ConclusionThese results establish an effective imaging technique that can track CAR T cells in GBM models and validate their early therapeutic effects, which may guide the evaluation of CAR T-cell therapies in solid tumors. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
