Allogeneic HLA-Matched Donor Dendritic Cells Loaded with Patient Leukemic Blasts Preferentially Induce CD4-Positive Leukemia-Reactive Donor LymphocytesThomas-Kaskel A.-K. · Alves Portugal T.G. · Herchenbach D. · Houet L. · Veelken H. · Finke J.
Department of Internal Medicine I, Hematology and Oncology, Freiburg University Medical Center, Freiburg, Germany
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 IFNγ 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.
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