TY  - JOUR
A1  - Kuçi, Selim
A1  - Rettinger, Eva
A1  - Voß, Bernhard
A1  - Weber, Gerrit
A1  - Stais, Miriam
A1  - Kreyenberg, Hermann
A1  - Willasch, Andre Manfred
A1  - Kuçi, Zyrafete
A1  - Koscielniak, Ewa
A1  - Klöß, Stephan
A1  - Laer, Dorothee von
A1  - Klingebiel, Thomas
A1  - Bader, Peter
T1  - Efficient lysis of rhabdomyosarcoma cells by cytokine-induced killer cells : implications for adoptive immunotherapy after allogeneic stem cell transplantation
T2  - Haematologica
N2  - Background: Rhabdomyosarcoma is the most common soft tissue sarcoma in childhood and has a poor prognosis. Here we assessed the capability of ex vivo expanded cytokine-induced killer cells to lyse both alveolar and embryonic rhabdomyosarcoma cell lines and investigated the mechanisms involved.

Design and Methods: Peripheral blood mononuclear cells from six healthy donors were used to generate and expand cytokine-induced killer cells. The phenotype and composition of these cells were determined by multiparameter flow cytometry, while their cytotoxic effect against rhabdomyosarcoma cells was evaluated by a europium release assay.

Results: Cytokine-induced killer cells efficiently lysed cells from both rhabdomyosarcoma cell lines. Antibody-mediated masking of either NKG2D molecule on cytokine-induced killer cells or its ligands on rhabdomyosarcoma cells (major histocompatibility antigen related chain A and B and UL16 binding protein 2) diminished this effect by 50%, suggesting a major role for the NKG2D molecule in rhabdomyosarcoma cell killing. No effect was observed after blocking CD11a, CD3 or TCRαβ molecules on cytokine-induced killer cells or CD1d on rhabdomyosar-coma cells. Remarkably, cytokine-induced killer cells used tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) to activate caspase-3, as the main caspase responsible for the execution of apoptosis. Accordingly, blocking TRAIL receptors on embryonic rhabdomyosarcoma cell lines significantly reduced the anti-tumor effect of cytokine-induced killer cells. About 50% of T cells within the cytokine-induced killer population had an effector memory phenotype, 20% had a naïve phenotype and approximately 30% of the cells had a central memory phenotype. In addition, cytokine-induced killer cells expressed low levels of activation-induced markers CD69 and CD137 and demonstrated a low alloreactive potential.

Conclusions: Our data suggest that cytokine-induced killer cells may be used as a novel adoptive immunotherapy for the treatment of patients with rhabdomyosarcoma after allogeneic stem cell transplantation.
Y1  - 2010
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/26600
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-266005
SN  - 1592-8721
SN  - 0390-6078
VL  - 95
IS  - 9
SP  - 1579
EP  - 1586
PB  - Ferrata Storti Foundation
CY  - Pavia
ER  -