Allogeneic HLA-matched donor dendritic cells loaded with patient leukemic blasts preferentially induce CD4-positive leukemia-reactive donor lymphocytes.
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.
Thomas-Kaskel
Anna-Katharina
AK
Department of Internal Medicine I, Hematology and Oncology, Freiburg University Medical Center, Freiburg, Germany. kaskel@mm11.ukl.uni-freiburg.de
Portugal
Tatiana Gil Alves
TG
Herchenbach
Dieter
D
Houet
Leonora
L
Veelken
Hendrik
H
Finke
Jürgen
J
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
D007371:Interferon-gamma