Project Details
Projekt
KFO 183: Optimised Allogeneic Lymphocyte Therapy
Subject Area
Medicine
Term
from 2007 to 2016
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 34036658
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.
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
- Cytomegalievirus (CMV)-spezifische CD4+ und CD8+ T-Zellen durch T-Zell-Rezeptor RNA Transfer (Applicant Thomas, Simone )
- Etablierung eines Challenge-Modells zur Optimierung der Immuntherapie von Cytomegalovirus-Erkrankungen (Applicant Plachter, Bodo )
- Etablierung eines Challenge-Modells zur Optimierung der Immuntherapie von Cytomegalovirus-Erkrankungen (Applicant Reddehase, Matthias J. )
- Etablierung eines human-murinen NOD/SCID/ycnull-Transplantationsmodells zur Evaluierung der antileukämischen Aktivität von NK Zellen (Applicant André, Maya Caroline )
- 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 )
- Generierung von leukämiereaktiven Spender-T-Zellen für die adoptive Immuntherapie (Applicant Distler, Eva )
- Identifizierung von Zielantigenen alloreaktiver zytotoxischer T-Zellen mittels cDNA-Expressionsklonierung (Applicant Wölfel, Catherine )
- Koordination der Klinischen Forschungsgruppe 183 (Applicant Herr, Wolfgang )
- Modulation von Graft-versus-Host und Graft-versus-Tumor Reaktionen durch regulatorische T-Zellen (Applicant Radsak, Markus P. )
- Molekulare T-Zelltherapie in der allogenen hämatopoetischen Stammzelltransplantation (Applicant Voss, Ralf-Holger )
- Molekulare T-Zelltherapie in der allogenen hämatopoetischen Stammzelltransplantation (Applicant Echchannaoui, Hakim )
- Zentrale Beantragung der Kosten für Versuchstiere (Applicant Reddehase, Matthias J. )
Leader
Professor Dr. Wolfgang Herr
Spokesperson
Professor Dr. Matthias Theobald
