title: Establishment of a murine graft-versus-myeloma model using allogeneic stem cell transplantation.
abstract: BACKGROUND
  Multiple myeloma (MM) is a malignant plasma cell disorder with poor long-term survival and high recurrence rates. Despite evidence of graft-versus-myeloma (GvM) effects, the use of allogeneic hematopoietic stem cell transplantation (allo-SCT) remains controversial in MM. In the current study, we investigated the anti-myeloma effects of allo-SCT from B10.D2 mice into MHC-matched myeloma-bearing Balb/cJ mice, with concomitant development of chronic graft-versus-host disease (GvHD).
  
  
  RESULTS
  Balb/cJ mice were injected intravenously with luciferase-transfected MOPC315.BM cells, and received an allogeneic (B10.D2 donor) or autologous (Balb/cJ donor) transplant 30 days later. We observed a GvM effect in 94% of the allogeneic transplanted mice, as the luciferase signal completely disappeared after transplantation, whereas all the autologous transplanted mice showed myeloma progression. Lower serum paraprotein levels and lower myeloma infiltration in bone marrow and spleen in the allogeneic setting confirmed the observed GvM effect. In addition, the treated mice also displayed chronic GvHD symptoms. In vivo and in vitro data suggested the involvement of effector memory CD4 and CD8 T cells associated with the GvM response. The essential role of CD8 T cells was demonstrated in vivo where CD8 T-cell depletion of the graft resulted in reduced GvM effects. Finally, TCR Vβ spectratyping analysis identified Vβ families within CD4 and CD8 T cells, which were associated with both GvM effects and GvHD, whereas other Vβ families within CD4 T cells were associated exclusively with either GvM or GvHD responses.
  
  
  CONCLUSIONS
  We successfully established an immunocompetent murine model of graft-versus-myeloma. This is the first murine GvM model using immunocompetent mice that develop MM which closely resembles human MM disease and that are treated after disease establishment with an allo-SCT. Importantly, using TCR Vβ spectratyping, we also demonstrated the presence of GvM unique responses potentially associated with the curative capacity of this immunotherapeutic approach.
authors.affiliation: Laboratory of Hematology, GIGA-Research, University of Liège, Liège, Belgium.
authors.forename: Marilène
authors.initials: M
authors.lastname: Binsfeld
authors.affiliation: Laboratory of Hematology, GIGA-Research, University of Liège, Liège, Belgium.
authors.forename: Yves
authors.initials: Y
authors.lastname: Beguin
authors.affiliation: Laboratory of Hematology, GIGA-Research, University of Liège, Liège, Belgium.
authors.forename: Ludovic
authors.initials: L
authors.lastname: Belle
authors.affiliation: Laboratory of Hematology, GIGA-Research, University of Liège, Liège, Belgium.
authors.forename: Eléonore
authors.initials: E
authors.lastname: Otjacques
authors.affiliation: Laboratory of Hematology, GIGA-Research, University of Liège, Liège, Belgium.
authors.forename: Muriel
authors.initials: M
authors.lastname: Hannon
authors.affiliation: Laboratory of Hematology, GIGA-Research, University of Liège, Liège, Belgium.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Briquet
authors.affiliation: Laboratory of Hematology, GIGA-Research, University of Liège, Liège, Belgium.
authors.forename: Roy
authors.initials: R
authors.lastname: Heusschen
authors.affiliation: University of Liège, Liège, Belgium.
authors.forename: Pierre
authors.initials: P
authors.lastname: Drion
authors.affiliation: John Theurer Cancer Center, Hackensack University Medical Center, Hackensack, New Jersey, United States of America.
authors.forename: Jenny
authors.initials: J
authors.lastname: Zilberberg
authors.affiliation: Centre for Immune Regulation, Institute of Immunology, University of Oslo and Oslo University Hospital, Oslo, Norway; KG Jebsen centre for research on influenza vaccines, Institute of Immunology, University of Oslo and Oslo University Hospital, Oslo, Norway.
authors.forename: Bjarne
authors.initials: B
authors.lastname: Bogen
authors.affiliation: Laboratory of Hematology, GIGA-Research, University of Liège, Liège, Belgium.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Baron
authors.affiliation: Laboratory of Hematology, GIGA-Research, University of Liège, Liège, Belgium.
authors.forename: Jo
authors.initials: J
authors.lastname: Caers
mesh_terms: D064591:Allografts; D000818:Animals; D005260:Female; D020350:Graft vs Tumor Effect / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009101:Multiple Myeloma / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D009374:Neoplasms, Experimental / Q000276:immunology / Q000473:pathology / Q000628:therapy*