title: Allogeneic HLA-matched donor dendritic cells loaded with patient leukemic blasts preferentially induce CD4-positive leukemia-reactive donor lymphocytes.
abstract: BACKGROUND
  The therapeutic value of donor lymphocyte infusions in patients who relapse with acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (HSCT) is limited by a low efficacy and the risk of graft-versus-host disease. We aimed at generating leukemia-reactive donor T cells for patients with AML.
  
  
  METHODS
  Peripheral blood mononuclear cells of the donor were stimulated with mature donor dendritic cells, pulsed with irradiated patient leukemic blasts (LB), or directly with cytokine-treated LB. After 3 weekly stimulations, donor cells were tested for anti-leukemic reactivity in an IFNgamma Elispot.
  
  
  RESULTS
  In 5 of 6 donors, cells with reactivity against patient LB with low or absent reactivity against non-leukemic cells could be generated. T cell subset analyses in 2 donors indicated that specific anti-leukemic reactivity was mainly mediated by CD4+ T cells, which were also the predominant cell fraction in 4 of 6 donors. One leukemia-reactive donor T cell line was expanded with a recently developed system. One week of expansion resulted in a 10-fold increase in reactivity with sustained specificity of the resulting T cell line.
  
  
  CONCLUSIONS
  Our results show the feasibility of the in vitro generation of leukemia-reactive donor lymphocytes, rendering this method a promising tool for post-HSCT immunotherapy.
authors.affiliation: Department of Internal Medicine I, Hematology and Oncology, Freiburg University Medical Center, Freiburg, Germany. kaskel@mm11.ukl.uni-freiburg.de
authors.forename: Anna-Katharina
authors.initials: AK
authors.lastname: Thomas-Kaskel
authors.forename: Tatiana Gil Alves
authors.initials: TG
authors.lastname: Portugal
authors.forename: Dieter
authors.initials: D
authors.lastname: Herchenbach
authors.forename: Leonora
authors.initials: L
authors.lastname: Houet
authors.forename: Hendrik
authors.initials: H
authors.lastname: Veelken
authors.forename: Jürgen
authors.initials: J
authors.lastname: Finke
mesh_terms: D000328:Adult; D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002455:Cell Division; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000637:transplantation*; D005260:Female; D006650:Histocompatibility Testing; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000378:metabolism; D007938:Leukemia / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D008214:Lymphocytes / Q000166:cytology / Q000276:immunology*; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D014184:Transplantation, Homologous
chemical_list: D007371:Interferon-gamma