An immunocompetent mouse model of human glioblastoma
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Samantha Semenkow1, Shen Li2,3, Ulf D. Kahlert4, Eric H. Raabe1,5, Jiadi Xu2, Antje Arnold2, Miroslaw Janowski2,3,6, Byoung Chol Oh7, Gerald Brandacher7, Jeff W.M. Bulte2,3, Charles G. Eberhart1,8 and Piotr Walczak2,3,9
1Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
2Russel H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
3Cellular Imaging Section and Vascular Biology Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
4Department of Neurosurgery, Heinrich-Heine-University Dusseldorf, Dusseldorf, Germany
5Division of Pediatric Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
6NeuroRepair Department, Mossakowski Medical Research Centre, PAS, Warsaw, Poland
7Department of Plastic and Reconstructive Surgery, Vascularized Composite Allotransplantation (VCA) Laboratory, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
8Department of Ophthalmology, The Johns Hopkins Medical Institute, Baltimore, MD, USA
9Department of Neurology, Faculty of Medical Sciences, University of Warmia and Mazury, Olsztyn, Poland
Piotr Walczak, email: [email protected]
Charles G. Eberhart, email: [email protected]
Keywords: brain tumor, human xenograft, costimulation blockade, immunocompetent, magnetic resonance imaging
Received: February 22, 2017 Accepted: April 05, 2017 Published: May 15, 2017
Orthotopic xenotransplantation studies represent the final stage in preclinical cancer research and could facilitate the implementation of precision medicine. To date, these xenografts have been tested in immunodeficient animals, but complete elimination of the adaptive immunity is a significant drawback. We present a method of efficient human glioblastoma (GBM) cell engraftment in adult mice with intact immune systems, mediated by a transient blockade of T-cell co-stimulation. Compared to transplants grown in immunodeficient hosts, the resulting tumors more accurately resemble the clinical pathophysiology of patient GBMs, which are characterized by blood-brain-barrier leakage and strong neo-vascularization. We expect our method to have great utility for studying human tumor cell biology, particularly in the field of cancer immunotherapy and in studies on microenvironmental interactions. Given the straightforward approach, the method may also be applicable to other tumor types and additional model organisms.
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