Oncotarget

Research Papers:

An immunocompetent mouse model of human glioblastoma

Samantha Semenkow, Shen Li, Ulf D. Kahlert, Eric H. Raabe, Jiadi Xu, Antje Arnold, Miroslaw Janowski, Byoung Chol Oh, Gerald Brandacher, Jeff W.M. Bulte, Charles G. Eberhart and Piotr Walczak _

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Oncotarget. 2017; 8:61072-61082. https://doi.org/10.18632/oncotarget.17851

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Abstract

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

Correspondence to:

Piotr Walczak, email: pwalczak@mri.jhu.edu

Charles G. Eberhart, email: ceberha@jhmi.edu

Keywords: brain tumor, human xenograft, costimulation blockade, immunocompetent, magnetic resonance imaging

Received: February 22, 2017     Accepted: April 05, 2017     Published: May 15, 2017

ABSTRACT

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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