Immunotherapies | Universitätsklinikum Tübingen

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

Approach

The continued central goal of the research area Immunotherapies (ImmT) will be the development of next generation immunotherapies. Pioneered by our former spokesperson Hans-Georg Rammensee and further advanced by his successor Juliane Walz, the immunopeptidome analysis of HLA-presented peptides will continue to be the backbone of the ImmT research program. Immunopeptidome-based antigen discovery will not only provide targets for peptide-based vaccines, but their corresponding T cells and T cell receptors (TCRs) will serve for the development of TCR-mimic CAR and TCR-like antibody constructs. The coordinators of this research area are Prof. Dr. Helmut Salih, Prof. Dr. Juliane Walz and Prof. Dr. Judith Feucht.

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

ImmT-1: Immunopeptidome-based Characterization of Next Generation Targets for
Cancer Immunotherapy
ImmT-2: Harnessing T Cell-mediated Immunity to Pathogens against Cancer
ImmT-3: Enhancing T cell Function Using Combinatorial Immunotherapies to Overcome Resistance

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.

This module builds on central advancements in mass spectrometry-based immunopeptidomics. Bringing together next generation mass spectrometry techniques as well as machine learning and AI approaches, we will set up a unique target discovery platform. Beyond characterizing HLA ligands for peptide-based vaccines, corresponding peptide-specific T cells and TCRs will be utilized for development of TCR-engineered and TCR-mimic CAR immune cell approaches and TCR-like antibody constructs.

ImmT-2

Driven by pioneering work of iFIT researchers during the COVID-19 pandemic, ImmT researchers will harness T cell-mediated immunity to pathogens to combat malignant disease. The team will unravel pathogen-related alternations of the tumor microenvironment and elucidate the mechanisms of the recently reported reinforcement of anti-tumor immunity upon infectious disease vaccination. This will guide the design of next generation anti-infectious vaccines that improve cancer immune surveillance. Antigens derived from microorganisms, in particular from microbiota and intertumoral bacteria with high homology to tumor antigens, represent natural targets of cancer immune surveillance and thus are promising novel candidates for immunotherapy development.

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.

iFIT researchers have established a unique bench-to-bedside pipeline for the development of personalized peptide-based vaccines, novel bispecific antibody formats and CAR-T cell concepts, with 12 approaches already undergoing evaluation within phase I and II clinical trials. A collaborative team of ImmT, FIMT and MFMI researchers will employ a reverse translation approach to take advantage from these trials to uncover and overcome mechanisms of resistance to T cell-based immunotherapy and develop novel combinatorial immunotherapeutic approaches.