SFB 643:
Strategies of Cellular Immune Intervention
Subject Area
Medicine
Biology
Term
from 2004 to 2016
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 5486111
Final Report Year
2016
Final Report Abstract
Immunological mechanisms play a pivotal role in numerous human diseases. The overall goal of our Collaborative Research Centre CRC 643 was the stepwise translation of basic immunologic findings into novel therapies based on manipulating the immune system. Our vision was to develop such novel immune intervention strategies to either stimulate insufficient immunity (as required to fight cancer or infections) or dampen undesirable immune responses (as in autoimmunity, allergy, and graft rejection). After twelve years of funding several novel targets and new immune intervention strategies have indeed been identified, and we are testing three of them already in the clinic. Advanced and universally applicable third generation "designer" dendritic cell (DC) based vaccines are used to induce enhanced immunity to cancer or infections. The adoptive transfer of virus-specific T cells or B cells is currently explored in clinical trials to fight virus infections which frequently occur after allogeneic stem cell transplantation and are still a major clinical problem. Besides these cellular therapies, two recombinant molecules have been developed to a stage allowing clinical testing in the near future, namely a dual-specificity antibody designed to attack leukemia cells optimally, and the so-called soluble CD83 molecule which can modulate immune reactions such as the ones causing rejection of allografts or autoimmunity. Members of the CRC also identified several new targets which will finally help to diagnose or treat common human diseases much better. Groundbreaking new basic immunology findings, e.g. that sodium ions not only regulate blood pressure but also regulate immune cells, have also been made and will find their way into textbooks and finally into clinical medicine.
DFG Programme
Collaborative Research Centres
Completed projects
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A01 - Identification of viral and cellular degradation signals that regulate MHC-I antigen presentation
(Project Head
Schubert, Ulrich
)
-
A02 - Rhadionvirales Ox-2 als Suppressor von Th1-Tyzokinwirkungen. Pathogenitische Bedeutung und Identifizierung therapeutischer Targets
(Project Head
Ensser, Armin
)
-
A03 - Zytotoxische T-Lymphozyten als Effektorzellen bei der Tuberkulose
(Project Head
Stenger, Steffen
)
-
A04 - Charakterisierung des CD83 Promotors zwecks gezielter Genexpression in reifen Dendritischen Zellen in vivo
(Project Head
Steinkasserer, Alexander
)
-
A05 - Induktion einer DZ-vermittelten Anti-Tumor-Immunantwort durch onkolytischer Adenoviren
(Project Head
Nettelbeck, Dirk M.
)
-
A06 - Activation, function and modulation of natural killer cells in mouse and human leishmaniasis
(Project Heads
Bogdan, Christian
;
Schleicher, Ulrike
)
-
A07 - Characterization of Dendritic cell functions in human tissues
(Project Head
Dudziak, Diana
)
-
A08 - Investigating the mechanism of antibody mediated effector functions in vivo
(Project Head
Nimmerjahn, Falk
)
-
A09 - ADAM17/10 loaded Microvesicles in Cancer; functional Analysis, diagnostic Tool and therapeutic Intervention
(Project Head
Baur, Andreas
)
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A10 - Dual specificity phosphatases in innate immunity
(Project Head
Lang, Roland
)
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A11 - Role of Thymic Stromal Lymphopoietin in Autoimmunity and Infection
(Project Head
Lechmann, Ph.D., Matthias
)
-
B01 - Interleukin-4 and IL-13 as therapeutic targets for immune intervention in infections and allergies
(Project Head
Gessner, Ph.D., André
)
-
B02 - Pharmakologische Beeinflussung des Th1/Th2-Gleichgewichtes
(Project Head
Pahl, Andreas
)
-
B03 - Selective modulation of the transcription factor NF-kB in regulatory T cells and dendritic cells as therapeutic strategies for the treatment of autoimmune diseases
(Project Head
Voll, Reinhard
)
-
B04 - Mechanismen der Induktion regulatorischer T-Zellen mittels Dendritischer Zellen in vivo
(Project Head
Lutz, Manfred
)
-
B05 - Immune modulation by ligands of dead and dying cells
(Project Head
Herrmann, Martin
)
-
B06 - Adoptiver Transfer von Cytomegalovirus-spezifischen Gedächtnis B-Zellen: Einfluss auf den Verlauf der Infektion und immunologische Mechanismen der sekundären Antikörperantwort
(Project Heads
Mach, Michael
;
Winkler, Thomas
)
-
B06 - Adoptive transfer of Cytomegalovirus-specific memory B cells: Mechnisms of protection
(Project Heads
Mach, Michael
;
Winkler, Thomas
)
-
B07 - Neu-entwickelte Sialinsäurederivate zur Verstärkung der B-Zellaktivierung über CD22 und deren möglicher therapeutischer Einsatz
(Project Head
Nitschke, Lars
)
-
B07 - Targeting of CD22 on B cell lymphoma cells and on B cells in autoimmune diseases
(Project Head
Nitschke, Lars
)
-
B08 - Determining the molecular pathways of the effects of regulatory T cells on monocytes/osteoclasts
(Project Head
Schett, Georg
)
-
B09 - Immune intervention in autoimmune disorders and transplantation using soluble CD83
(Project Heads
Steinkasserer, Alexander
;
Zinser, Elisabeth
)
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B10 - Modulation of dendritic cell entry into afferent lymphatics to prevent graft rejection after (corneal) transplantation
(Project Head
Cursiefen, Claus
)
-
B11 - Regulation and Pathogenetic Relevance of the IL-28/IL-28R Signaling Pathway in Experimental Colitis and Inflammatory Bowel Diseases
(Project Heads
Neurath, Markus F.
;
Siebler, Juergen
)
-
B12 - Immunoregulatory role of the transcription factor NFAT in airway inflammation and lung cancer
(Project Head
Finotto, Ph.D., Susetta
)
-
B13 - Induction of tumor-specific immune responses by combined transcriptional- and transductional targeting of DC in vivo
(Project Head
Steinkasserer, Alexander
)
-
B14 - Investigating the mechanism of antibody mediated effector functions in vivo
(Project Head
Nimmerjahn, Falk
)
-
B15 - T cell homeostasis and effector functions under lymphopenic conditions
(Project Head
Vöhringer, David
)
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B16 - Regulation of the internal electrolyte micromilieu by the immune system during homeostasis and inflammation
(Project Heads
Jantsch, Jonathan
;
Titze, Jens Marc
)
-
C01 - Optimizing vaccination with mRNA-transfected Dendritic Cells by evaluating concepts in vitro
(Project Heads
Schaft, Ph.D., Niels
;
Schuler, Gerold
;
Schuler-Thurner, Beatrice
)
-
C02 - Identifikation einer optimalen Strategien zur Beladung dendritischer Zellen mit dem gesamten antigenen Repertoire von Tumorzellen: Vergleich von RNA-Transfektion und Aufnahme apoptotischer Partikel opsonisiert mit rekombinanten bispezifischen Antikörpern
(Project Heads
Fey, Georg H.
;
Kämpgen, Eckhart
)
-
C05 - Induktion einer Toleranz durch Identifizierung tolerogener T-Zellepitope bei der Sprue
(Project Head
Dieterich, Walburga
)
-
C06 - Bivalent recombinant antibody-derivates for the elimination of malignant AML cells
(Project Head
Fey, Georg H.
)
-
C08 - Adoptive transfer of CMV/EBV multi-epitope specific T-cells for prevention and treatment of virus reactivation in patients after matched allogeneic stem cell transplantation
(Project Heads
Aigner, Michael
;
Gerbitz, Armin
;
Mackensen, Andreas
)
-
C09 - Adoptive Transfer of cytomegalovirus-specific memory B-cells: Implementation of a Phase I/IIa clinical study
(Project Heads
Mach, Michael
;
Winkler, Thomas
;
Winkler, Julia
)
-
MGK - Integrated Research Training Group (IRTG)
(Project Heads
Herrmann, Martin
;
Schleicher, Ulrike
)
-
Z01 - Central Tasks
(Project Head
Schuler, Gerold
)
-
Z02 - Core Unit for Cell Sorting and Immuno-monitoring
(Project Head
Schuler, Gerold
)