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: Anna-Katharina Thomas-Kaskel, Tatiana Gil Alves Portugal, Dieter Herchenbach, Leonora Houet, Hendrik Veelken, Jürgen Finke
• Journal: Acta haematologica (Acta Haematol) Vol. 117 Issue 4 Pg. 226-35 ( 2007) ISSN: 1421-9662 [Electronic] Switzerland
• PMID: 17308369 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: 2007 S. Karger AG, Basel

Chemical References

• Interferon-gamma

Topics

• Adult
• Aged
• CD4-Positive T-Lymphocytes (immunology)
• Cell Division
• Cell Line, Tumor
• Dendritic Cells (transplantation)
• Female
• Histocompatibility Testing
• Humans
• Immunophenotyping
• Interferon-gamma (metabolism)
• Leukemia (immunology, metabolism, therapy)
• Lymphocytes (cytology, immunology)
• Male
• Microscopy, Confocal
• Middle Aged
• Transplantation, Homologous