SFB 738:  Optimisation of Conventional and Innovative Transplants

• Subject Area: Medicine
• Term: from 2007 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 24899777

Organ transplantation still remains the only life-saving treatment option for patients with advanced organ dysfunction. Despite improvement in short-term survival, chronic graft loss, morbidity and mortality caused by immunosuppression (IS) remain major clinical obstacles. This has currently been aggravated by an increased shortage of donor organs and use of an increasing number of marginal donor organs. The aim of the Collaborative Research Centretherefore is (1) to reduce the need for transplantation by improving therapy of end stage organ disease, (2) to improve transplantation outcomes by reducing transplant associated morbidity and mortality, (3) to achieve a longer graft survival in order to reduce the need for retransplantation and (4) to improve the patient¿s quality of life.Recurrent leukemia after hematopoietic stem cell (HSC) transplantation remains a major clinical problem limiting the clinical success. Therefore, new effective interventions to achieve a better graft versus leukemia (GvL) response are urgently needed. However, patients receiving allogeneic HSC transplantation suffer from the risk of graft versus host disease (GvHD) development, which also causes significant morbidity. The Collaborative Research Centre therefore aims at improving GvL without causing GvHD. Methods to improve immune reconstitution after HSC transplantation to reduce the number of infectious diseases are also investigated within the Collaborative Research Centre.New specific therapeutic interventions often rely on innovative advanced medicinal therapy products (ATMPs) based on combined gene and cell therapy. Collaborative Research Centre seeks to improve cellular and molecular interventions to achieve the above-mentioned goals. In addition,Collaborative Research Centre aims to develop cellular transplantation as an alternative to classical full solid organ transplantation. These new modalities do not rely on donor organs and could even be performed in an autologous setting without the need for unspecific immunosuppression. Careful modulation of the delicate balance between immunity and tolerance is of major importance in solid organ and HSC transplantation. The goal of Collaborative Research Centre is to achieve long-lasting, tissue-specific tolerance without interfering with the overall competence of the patien´s immune system.

• DFG Programme: Collaborative Research Centres

Completed projects

• A01 - Transcriptional control of regulatory T-cells in the allogeneic immune response (Project Heads Buer, Jan ;  Franzke, Anke )
• A02 - Proteomics applied to the investigation of tolerance and the pathophysiology of graft-versus-host disease post-allogeneic stem cell transplantation (Project Heads Ganser, Arnold ;  Mischak-Weissinger, Eva )
• A03 - The thymic gate: The role of thymic selection processes for cotransplantation of CAR-engineered precursor T-cells for leukemia control after mismatched hematopoietic stemcell transplantation (Project Head Sauer, Martin )
• A04 - Mechanisms and reversion of leukemia-induced tolerance in murine model systems (Project Head Klein, Christoph )
• A05 - Natural immune regulation in transplantation (Project Heads Jacobs, Roland ;  Schmidt, Reinhold Ernst )
• A06 - Lentiviral vector reprogrammed dendritic cells for immune reconstitution of T- and B-cells after allogeneic stem cell transplantation and protection against HCMV (Project Heads Messerle, Martin ;  Stripecke, Ph.D., Renata )
• A07 - Molecular mechanisms of miRNA-mediated control of T-cell regeneration after hematopoietic stem cell transplantation (Project Head Krueger, Andreas )
• A08 - Prevention of acute Graft-versus-Host disease after allogeneic stem cell transplantation by molecular targeting of anti-apoptotic proteins in activated donor T-cells (Project Heads Eder, Matthias ;  Könecke, Christian )
• B01 - Role of regulatory T-cells in the development of donor-specific adaptation after clinical organ transplantation (Project Heads Klempnauer, Jürgen ;  Schwinzer, Reinhard )
• B02 - Immunological and viral determinants of graft hepatitis C after liver transplantation in the context of novel antiviral therapies (Project Heads Ciesek, Sandra ;  Cornberg, Markus ;  Greten, Tim F. ;  von Hahn, Thomas ;  Wedemeyer, Heiner )
• B03 - T- and NK-cell-mediated immune responses of human lung transplant recipients in vivo - impact on the development of transplant arteriosclerosis (Project Heads Falk, Christine ;  Warnecke, Gregor )
• B04 - Graft-specific tolerance after transplantation (Project Head Jaeckel, Elmar )
• B05 - Spatio-temporal distribution of immune cells during chronic organ rejection (Project Head Förster, Reinhold )
• B06 - Polymorphic glycoproteins of the cytomegalovirus RL11 family - significance for the CMV disease in transplant recipients (Project Head Messerle, Martin )
• B07 - Mechanisms of epithelial deterioration in renal allograft rejection (Project Head Einecke, Gunilla )
• B08 - The role of the activating receptors CD6 and DNAM-1 for human NK cell function in solid organ transplantation (Project Head Falk, Christine )
• B09 - Inflammation and fibrogenesis in early lesions of chronic lung allograft dysfunction (Project Heads Jonigk, Danny David ;  Länger, Florian Peter )
• C01 - Hepatic progenitor cells as a source for cell transplantation (Project Head Malek, Nisar Peter )
• C02 - Analysis of alterations of micro- and macroenvironment of the stem cell niche caused by telomere dysfunction (Project Head Rudolph, Karl Lenhard )
• C03 - Lentiviral vector induced insertional mutagenesis in gene therapy of hereditary liver disease (Project Heads Modlich, Ph.D., Ute ;  Ott, Michael )
• C04 - Reversible cell modification by transfer of proteins, mRNA, DNA to optimize transplantation (Project Heads Baum, Christopher ;  Bode, Jürgen ;  Galla, Melanie ;  Moritz, Thomas )
• C05 - Recruitment and activation of mesenchymal cells in renal allografts (Project Heads Bock, Oliver ;  Kreipe, Hans ;  Mengel, Michael )
• C07 - Generation of stable, alloantigen-specific Foxp3+ regulatory T-cells (Project Head Hühn, Jochen )
• C08 - Interference with senescence-dependent mechanisms to improve renal transplant outcome (Project Heads Melk, Ph.D., Anette ;  Schmitt, Roland )
• C09 - Generation of therapeutically effective stem cell transplants by targeted genome modification (Project Heads Cathomen, Toni ;  Charpentier, Ph.D., Emmanuelle ;  Schambach, Axel )
• C10 - Dual-specific targeted NK cells post allogeneic stem cell transplantation to improve anticancer effect against myeloid leukemia stem cells (Project Head Köhl, Ulrike )
• C11 - Use of a pre-clinical pig model to characterize and modulate immune responses following liver cell transplantation (Project Heads Bock, Michael ;  Vondran, Florian )
• C12 - Elucidation of supportive microRNAs during hepatic specification of reprogrammed cells in liver cell therapy (Project Heads Cantz, Tobias ;  Sharma, Ph.D., Amar Deep )
• Z01 - Identification, isolation and molecular characterization of immunomodulatory cells (Project Heads Geffers, Ph.D., Robert ;  Jaeckel, Elmar )
• Z02 - Protocol biopsy program after kidney and liver transplantation for the SFB 738 (Project Heads Haller, Hermann ;  Haverich, Axel ;  Klempnauer, Jürgen ;  Kreipe, Hans ;  Manns, Michael Peter ;  Welte, Tobias )
• Z03 - General information (Project Heads Ganser, Arnold ;  Manns, Michael Peter )

• Applicant Institution: Medizinische Hochschule Hannover
• Participating Institution: Helmholtz-Zentrum für Infektionsforschung (HZI)
• Spokespersons: Professor Dr. Arnold Ganser, since 1/2019; Professor Dr. Michael Peter Manns, until 12/2018