Cancer research made in Tuebingen
iFIT Cluster of Excellence

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How can we decipher and at the same time overcome the mechanisms that mediate resistance to immunotherapies, especially in solid tumors?

The interaction between professorships, independent research groups and core units to facilitate projects and implement the overall research strategy defined in the ImmT is emphasized.

Approach

The Immunotherapies research area deals with the question of how innovative immunotherapies can contribute to activating the patient's own immune system against tumor cells and thus support targeted drug therapy. Prof. Dr. Hans-Georg Rammensee, former director of the Department of Immunology at the University of Tübingen and co-spokesperson of the cluster, and his team have carried out internationally pioneering work with the elucidation of the recognition mechanisms of the immune system's T-cells.

In addition to Prof. Dr. Rammensee, the coordinators of the research area are Prof. Dr. Helmut Salih and Prof. Dr. Juliane Walz. The latter has taken over the role of spokesperson following the retirement of Hans-Georg Rammensee and will continue the work on the development of peptide-based immunotherapies.

The research area "Immunotherapies" (ImmT) is divided into three research modules:

  • ImmT-1: Immunopeptidomics: The Role of Drug- or Stress-induced Physiological Adaptations and Peptide-specific T-cell Responses for Immunotherapy
  • ImmT-2: Improved Peptide Vaccinations: Optimizing Targets, T-cell Responses, Time Points and Adjuvants
  • ImmT-3: Novel Antibody Formats and Optimization of Antibody-based Recruitment of Cytotoxic Lymphocytes

ImmT-1

The cluster uses two state-of-the-art mass spectrometers that enable us to identify tumor-specific structures that are recognized by the immune system.

ImmT-1 works in close collaboration with FIMT to investigate the influence of cancer drugs and cell stress states on the target structures of the cancer immune response. These are peptides that can be recognized by T cells via human leukocyte antigens (HLA). Initial studies have shown that certain drugs and their mechanisms of action have a direct effect on the peptides and also lead to the induction of new so-called treatment-associated peptides, which represent promising target structures for combinatorial immunotherapies.

The second focus of ImmT-1 is to better understand immune-mediated resistance mechanisms against immune checkpoint inhibitors in order to identify new biomarkers and therapies.

ImmT-2

The ImmT-2 research module focuses on the development of optimized therapeutic cancer vaccines. For this purpose, two indispensable prerequisites for clinically effective vaccine development are addressed:

(i) the identification and characterization of naturally presented tumor antigens (peptides) that are applicable for both personalized approaches and large patient cohorts. For the selection of naturally presented antigens, iFIT uses the mass spectrometric (MS) immunopeptidome analysis technology developed by Hans-Georg Rammensee, which, thanks to groundbreaking developments by Tübingen scientists in recent years, enables the identification of suitable mutated and non-mutated antigens for immunotherapy approaches from the smallest tumor samples in a short period of time

(ii) an optimal adjuvant for the induction of potent and long-lasting T-cell responses. Here, a first TLR 1/2 ligand was developed by iFIT scientists which is characterized as a new promising adjuvant XS15 both preclinically and in first successful studies and enables for the first time the induction of highly potent and long-lasting T cell responses in cancer patients.

Schematic representation of the central role of MHC-presented peptides for immune reactions triggered by checkpoint-blocking antibodies.

ImmT-3

In contrast to other antibodies, bispecific antibodies can simultaneously bind to two different surface features and thus bring tumor cells and the immune cells fighting them together.

The ImmT-3 research module focuses on the development of new antibody constructs to overcome current limitations of T cell-based immunotherapies in solid tumors, including

The lack of tumor accessibility to effector cells: This limitation could be overcome by dual targeting of the tumor vasculature and the tumor cells themselves.

Inherent resistance of tumor cells to attack by cytotoxic T lymphocytes: This could be overcome by combining immunotherapy with (molecular) treatment modalities to overcome treatment resistance.

Lack of sustainability of the therapeutically induced immune response: In addition to the use of appropriate adjuvants as described above, we aim to overcome this limitation by approaches such as target cell-restricted co-stimulation with novel bispecific antibodies.

The development of these constructs and their application by MFMI will be supported by new imaging techniques that guide patient selection and therapy monitoring.

Principal & Associated Investigators

Prof. Dr. Bernd Pichler

Direktor Präklinische Bildgebung und Radiopharmazie

Phone number: +49 7071 29-83427

E-mail address: bernd.pichler@med.uni-tuebingen.de

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Prof. Dr. Helmut Salih

Ärztlicher Direktor KKE Translationale Immunologie

Phone number: +49 7071 29 83275

Fax number: 07071 29 4391

E-mail address: helmut.salih@med.uni-tuebingen.de

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Prof. Dr. Juliane Walz

Medizinische Direktorin
KKE Translationale Immunologie

Phone number: +49 7071 29-87305

E-mail address: juliane.walz@med.uni-tuebingen.de

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Prof. Dr.med Dr. rer.nat. Ghazaleh Tabatabai

Prof. Dr.med Dr. rer.nat. Ghazaleh Tabatabai

Ärztliche Direktorin, Abteilung Neurologie mit Interdisziplinärem Schwerpunkt Neuroonkologie

Phone number: +49 7071 29-85018

Fax number: 07071 29-25167

E-mail address: ghazaleh.tabatabai@med.uni-tuebingen.de

Publications: Publications

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Dr. med. Judith Feucht

Dr. med. Judith Feucht

Ärztin und Arbeitsgruppenleiterin

E-mail address: judith.feucht@med.uni-tuebingen.de

Publications: Publications

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Jun. Prof. Dr. med. Josef Leibold

Jun. Prof. Dr. med. Josef Leibold

Juniorprofessor für Functional Immunogenomics

Phone number: +49 7071 29-82711

E-mail address: josef.leibold@med.uni-tuebingen.de

Publications: Publications

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Dr. Annika Nelde

Dr. Annika Nelde

Bereichsleitung Forschung

Phone number: +49 7071 29-78685

E-mail address: annika.nelde@uni-tuebingen.de

Publications: Publications

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Prof. Dr. Lukas Flatz

Prof. Dr. Lukas Flatz

Oberarzt, Sektionsleiter Dermato-Onkologie

E-mail address: lukas.flatz@med.uni-tuebingen.de

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Dr. med. Benjamin Ruf

Dr. med. Benjamin Ruf

Arzt in Weiterbildung & Arbeitsgruppenleiter

E-mail address: benjamin.ruf@med.uni-tuebingen.de

Publications: PubMed

Publications: Google Scholar

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Dr. Marissa Dubbelaar

Dr. Marissa Dubbelaar

Leitung Bioinformatik

Phone number: +49 7071 29-78288

E-mail address: marissa.dubbelaar@uni-tuebingen.de

Publications: Google Scholar

Publications: ResearchGate

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Prof. Dr. rer. nat. Lisa Sevenich

Prof. Dr. rer. nat. Lisa Sevenich

Arbeitsgruppenleiterin

Phone number: +49 7071 29-82514

E-mail address: lisa.sevenich@med.uni-tuebingen.de

Publications: Publikationen

Publications: Publications

Publications: Publications

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Dr. Florian Wimmers

Gruppen Leiter

Institution: Department for Molecular Medicine
Interfaculty Institute for Biochemistry
University of Tübingen

E-mail address: Florian.Wimmers@med.uni-tuebingen.de

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Prof. Dr. rer. nat. Sven Nahnsen

Professur für Biomedical Data Science, Universität Tübingen

Institution: Zentrum für Quantitative Biologie (QBiC)
Forschungsinstitut M3

E-mail address: sven.nahnsen@qbic.uni-tuebingen.de

Person profile: Mehr zur Person