The therapeutic success of allogeneic hematopoietic stem cell transplantation (HSCT) in patients with hematologic malignancies relies primarily on the specificity and the functional activity of the donor T lymphocytes. They mediate not only the desired graft-versus-leukemia effect (GvL) but contribute also significantly to alloreactivity against epithelial tissues clinically known as the graft-versus-host disease (GvHD). In addition, donor T lymphocytes lacking an effective immunity against human cytomegalovirus (HCMV) favour the reactivation of HCMV infections in HCMV-positive patients after allogeneic HSCT. Natural killer (NK) cells of donor origin play also an important role post-transplant. For instance, they execute alloreactive GvL reactions after HSCT in HLA-incompatible donor-recipient pairs.
The Clinical Research Unit introduced herein desires to pursue the development of new immunomodulatory strategies that optimise these key functions of donor T cells and NK cells for the clinical implementation in the context of allogeneic HSCT. These strategies include the selective depletion of alloreactive T cells to reduce GvHD, the augmentation of the GvL effect by T cells and NK cells in order to avoid leukemia relapse and the induction of protective immunity for the prevention and therapy of HCMV infections.
DFG Programme
Clinical Research Units
International Connection
Netherlands
Projects
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Cytomegalievirus (CMV)-spezifische CD4+ und CD8+ T-Zellen durch T-Zell-Rezeptor RNA Transfer
(Applicant
Thomas, Simone
)
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Etablierung eines Challenge-Modells zur Optimierung der Immuntherapie von Cytomegalovirus-Erkrankungen
(Applicant
Plachter, Bodo
)
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Etablierung eines Challenge-Modells zur Optimierung der Immuntherapie von Cytomegalovirus-Erkrankungen
(Applicant
Reddehase, Matthias J.
)
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Etablierung eines human-murinen NOD/SCID/ycnull-Transplantationsmodells zur Evaluierung der antileukämischen Aktivität von NK Zellen
(Applicant
André, Maya Caroline
)
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Evaluation von T-Zell-vermittelter Graft-versus-Host- und Graft-versus-Leukämiereaktivität in einem chimären human-murinen NOD/SCID/yc null-Transplantationsmodell
(Applicant
Hartwig, Ph.D., Udo Frank
)
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Generierung von leukämiereaktiven Spender-T-Zellen für die adoptive Immuntherapie
(Applicant
Distler, Eva
)
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Identifizierung von Zielantigenen alloreaktiver zytotoxischer T-Zellen mittels cDNA-Expressionsklonierung
(Applicant
Wölfel, Catherine
)
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Koordination der Klinischen Forschungsgruppe 183
(Applicant
Herr, Wolfgang
)
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Modulation von Graft-versus-Host und Graft-versus-Tumor Reaktionen durch regulatorische T-Zellen
(Applicant
Radsak, Markus P.
)
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Molekulare T-Zelltherapie in der allogenen hämatopoetischen Stammzelltransplantation
(Applicant
Voss, Ralf-Holger
)
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Molekulare T-Zelltherapie in der allogenen hämatopoetischen Stammzelltransplantation
(Applicant
Echchannaoui, Hakim
)
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Zentrale Beantragung der Kosten für Versuchstiere
(Applicant
Reddehase, Matthias J.
)
