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Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
The quality and quantity of leukemia-derived dendritic cells from patients with acute myeloid leukemia and myelodysplastic syndrome are a predictive factor for the lytic potential of dendritic cells-primed leukemia-specific T Cells.
J. Immunother. 33, 523-527 (2010)
Adoptive immunotherapy is an important therapy option to reduce relapse rates after stem-cell transplantation in patients suffering from acute myeloid leukemia and myelodysplastic syndromes. Myeloid leukemic cells can regularly be induced to differentiate into leukemia-derived dendritic cells (DCleu), regaining the stimulatory capacity of professional dendritic cells (DCs) while presenting the known/unknown leukemic antigen repertoire. So far, induced antileukemic T-cell responses are variable or even mediate opposite effects. To further elicit DC/DCleu-induced T-cell-response patterns, we generated DC from 17 Acute myeloid leukemia (AML) and 2 myelodysplastic syndrome cases and carried out flowcytometry and (functional) nonradioactive fluorolysis assays before/after mixed lymphocyte cultures of matched (allogeneic) donor T cells (n = 6), T cells prepared at relapse after stem-cell transplantation (n = 4) or (autologous) patients' T cells (n = 7) with blast containing mononuclear cells ("MNC") or DCleu ("DC"). Compared with "MNC", "DC" were better mediators of antileukemic-activity, although not in every case effective. We could define DC subtypes and cut-off proportions of DC subtypes/qualities (mature DC/DCleu) after "DC" priming, which were predictive for an antileukemic activity of primed T cells and the clinical course of the disease after immunotherapy (allogeneic stem-cell transplantation/donor lymphocytes infusion/therapy). In summary, our data show that the composition and quality of DC after a mixed lymphocyte culture-priming phase is predictive for a successful ex vivo antileukemic response, especially with respect to proportions of mature and leukemia-derived DC. These data contribute not only to predict DC-mediated functions or the clinical course of the diseases but also to develop and refine DC-vaccination strategies that may pave the way to develop and modify adoptive immunotherapy, especially for patients at relapse after allogeneic stem-cell transplantation.
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
acute myeloid leukemia; dendritic cells; serum free culture; T cells; Immunotherapy
ISSN (print) / ISBN
1524-9557
e-ISSN
1537-4513
Zeitschrift
Journal of Immunotherapy
Quellenangaben
Band: 33,
Heft: 5,
Seiten: 523-527
Verlag
Lippincott Williams & Wilkins
Verlagsort
Philadelphia
Begutachtungsstatus
Peer reviewed
Institut(e)
CCG Hematopoetic Cell Transplants (IMI-KHZ)