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, Piotr Walczak

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)61072-61082
Number of pages11
JournalOncotarget
Volume8
Issue number37
DOIs
StatePublished - Sep 1 2017

Keywords

  • Brain tumor
  • Costimulation blockade
  • Human xenograft
  • Immunocompetent
  • Magnetic resonance imaging

ASJC Scopus subject areas

  • Oncology

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