title: Ewing sarcoma dissemination and response to T-cell therapy in mice assessed by whole-body magnetic resonance imaging.
abstract: BACKGROUND
  Novel treatment strategies in Ewing sarcoma include targeted cellular therapies. Preclinical in vivo models are needed that reflect their activity against systemic (micro)metastatic disease.
  
  
  METHODS
  Whole-body magnetic resonance imaging (WB-MRI) was used to monitor the engraftment and dissemination of human Ewing sarcoma xenografts in mice. In this model, we evaluated the therapeutic efficacy of T cells redirected against the Ewing sarcoma-associated antigen GD2 by chimeric receptor engineering.
  
  
  RESULTS
  Of 18 mice receiving intravenous injections of VH-64 Ewing sarcoma cells, all developed disseminated tumour growth detectable by WB-MRI. All mice had lung tumours, and the majority had additional manifestations in the bone, soft tissues, and/or kidney. Sequential scans revealed in vivo growth of tumours. Diffusion-weighted whole-body imaging with background signal suppression effectively visualised Ewing sarcoma growth in extrapulmonary sites. Animals receiving GD2-targeted T-cell therapy had lower numbers of pulmonary tumours than controls, and the median volume of soft tissue tumours at first detection was lower, with a tumour growth delay over time.
  
  
  CONCLUSIONS
  Magnetic resonance imaging reliably visualises disseminated Ewing sarcoma growth in mice. GD2-retargeted T cells can noticeably delay tumour growth and reduce pulmonary Ewing sarcoma manifestations in this aggressive disease model.
authors.affiliation: Department of Clinical Radiology, University Hospital Muenster, Muenster, Germany.
authors.forename: L
authors.initials: L
authors.lastname: Liebsch
authors.forename: S
authors.initials: S
authors.lastname: Kailayangiri
authors.forename: L
authors.initials: L
authors.lastname: Beck
authors.forename: B
authors.initials: B
authors.lastname: Altvater
authors.forename: R
authors.initials: R
authors.lastname: Koch
authors.forename: C
authors.initials: C
authors.lastname: Dierkes
authors.forename: M
authors.initials: M
authors.lastname: Hotfilder
authors.forename: N
authors.initials: N
authors.lastname: Nagelmann
authors.forename: C
authors.initials: C
authors.lastname: Faber
authors.forename: H
authors.initials: H
authors.lastname: Kooijman
authors.forename: J
authors.initials: J
authors.lastname: Ring
authors.forename: V
authors.initials: V
authors.lastname: Vieth
authors.forename: C
authors.initials: C
authors.lastname: Rossig
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods; D005260:Female; D005732:Gangliosides / Q000276:immunology; D006801:Humans; D016219:Immunotherapy, Adoptive; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D012512:Sarcoma, Ewing / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D013601:T-Lymphocytes / Q000276:immunology*; D051598:Whole Body Imaging / Q000379:methods; D023041:Xenograft Model Antitumor Assays
chemical_list: D005732:Gangliosides; C019403:ganglioside, GD2