title: Adoptive transfer of genetically modified Wilms' tumor 1-specific T cells in a novel malignant skull base meningioma model.
abstract: BACKGROUND
  Meningiomas are the most commonly diagnosed primary intracranial neoplasms. Despite significant advances in modern therapies, the management of malignant meningioma and skull base meningioma remains a challenge. Thus, the development of new treatment modalities is urgently needed for these difficult-to-treat meningiomas. The goal of this study was to investigate the potential of build-in short interfering RNA-based Wilms' tumor protein (WT1)-targeted adoptive immunotherapy in a reproducible mouse model of malignant skull base meningioma that we recently established.
  
  
  METHODS
  We compared WT1 mRNA expression in human meningioma tissues and gliomas by quantitative real-time reverse-transcription polymerase chain reaction. Human malignant meningioma cells (IOMM-Lee cells) were labeled with green fluorescent protein (GFP) and implanted at the skull base of immunodeficient mice by using the postglenoid foramen injection (PGFi) technique. The animals were sacrificed at specific time points for analysis of tumor formation. Two groups of animals received adoptive immunotherapy with control peripheral blood mononuclear cells (PBMCs) or WT1-targeted PBMCs.
  
  
  RESULTS
  High levels of WT1 mRNA expression were observed in many meningioma tissues and all meningioma cell lines. IOMM-Lee-GFP cells were successfully implanted using the PGFi technique, and malignant skull base meningiomas were induced in all mice. The systemically delivered WT1-targeted PBMCs infiltrated skull base meningiomas and significantly delayed tumor growth and increased survival time.
  
  
  CONCLUSIONS
  We have established a reproducible mouse model of malignant skull base meningioma. WT1-targeted adoptive immunotherapy appears to be a promising approach for the treatment of difficult-to-treat meningiomas.
authors: Department of Neurosurgery, Nagoya University, Graduate School of Medicine, 65, Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
authors: Kenichiro
authors: K
authors: Iwami
authors: Atsushi
authors: A
authors: Natsume
authors: Masasuke
authors: M
authors: Ohno
authors: Hiroaki
authors: H
authors: Ikeda
authors: Junichi
authors: J
authors: Mineno
authors: Ikuei
authors: I
authors: Nukaya
authors: Sachiko
authors: S
authors: Okamoto
authors: Hiroshi
authors: H
authors: Fujiwara
authors: Masaki
authors: M
authors: Yasukawa
authors: Hiroshi
authors: H
authors: Shiku
authors: Toshihiko
authors: T
authors: Wakabayashi
mesh_terms: D019264:Adoptive Transfer; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D049109:Cell Proliferation; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D005818:Genetic Engineering; D006801:Humans; D007124:Immunoenzyme Techniques; D016219:Immunotherapy, Adoptive; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D008577:Meningeal Neoplasms / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D008579:Meningioma / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019292:Skull Base Neoplasms / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D013601:T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000473:pathology; D014407:Tumor Cells, Cultured; D025721:WT1 Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D025721:WT1 Proteins
keywords: Wilms' tumor 1; adoptive immunotherapy; cranial nerve; skull base meningioma