Applied Tumor Immunity

Our Research

The immune system influences the efficacy of many therapies and interventions. Thus, the identification of crucial immunological parameters, such as novel biomarkers, is of great importance. The aim of the Clinical Cooperation Unit (CCU) Applied Tumor Immunity is the characterization of immune responses directed against the tumor and the transfer of these findings into clinical applications. A particular focus of our research is the analysis of immunological interactions between tumor cells and host or immune cells in the tumor microenvironment and periphery to identify predictive biomarkers and develop novel immunotherapeutic approaches for solid tumors (e.g. TCR T cells, CAR T cells, bispecific antibodies and peptide vaccines).

In close collaboration with Prof. Jäger´s Department of Medical Oncology and other partners at the University Hospital Heidelberg (UKHD) and the Thoraxklinik Heidelberg we conduct innovative clinical trials and biomarker studies, such as the PROMISE trial.

Our current main focus lies on patient-tailored adoptivce T cell therapy (ACT). Together with the Department of Medical Oncology (UKHD), Prof. S. Eichmüller (DKFZ) and with strong support by the Dietmar-Hopp-Foundation we envision to establish a network in the area of immune and cellular therapies which integrates development, GMP production and administration. This will enable us to develop innovative therapy approaches and produce study drugs for Phase I trials at the NCT, the UKHD, for partner sites within the NCT network as well as to serve as manufacturer for approved cellular drugs.

Additional Research Groups within the CCU Applied Tumor Immunity

Tageted Tumor Vaccines
Head: Dr. Angel Cid-Arregui

Translational Research in Immuno-oncology and Microbiome (TRIM)
Head: Dr. Maria Paula Roberti

Cellular Therapies

Image of a full opto-electric chip analyzed in the Berkeley Lights Lightning System. Jurkat-CAR-Venus-reporter cells were penned into cavities in single clones and have been activated specifically. Serial image analysis has been performed constantly from 4 – 24h post activation. Representative image after 16h of activation is shown.

CAR-T cell immunotherapy

Adoptive T cell therapy using genetically engineered T cells expressing a chimeric antigen receptor (CAR) has revolutionized the treatment modalities in leukemia and lymphoma for more than a decade now. However, the translation of the successes to solid tumor diseases is rather slow. Within our team, we are dedicated to the development and manufacturing of novel and safe CARs that can be applied in the clinics. For instance, we have developed two novel CAR-T cell products for the use in breast cancer patients that target the cancer testis antigen NY-BR-1 and prevent cross-reactivity against healthy brain tissue. Our team analyzed both for efficiency and safety in vitro and in vivo in a xenotransplant and target transgenic mouse model.

In close collaboration with Dr. Richard Harbottle (DKFZ, DNA Vector Lab), we have developed a novel DNA-plasmid-based vector system for the GMP-grade manufacturing of CAR-T cells that makes the use of (lenti)viral vectors dispensable. These vectors, which we named nS/MARt, do not possess the risk of genotoxicity but confer the same characteristics as viral vectors, e.g. stable expression (Bozza M et al, 2021, SciAdv, 7(16):eabf1333). As a desired side effect, this novel manufacturing method will reduce overall costs for CAR-T cell production. In another project, we are developing novel, specific CAR inhibitors that can temporarily impair their function and therefore maybe useful to lower clinical side effects. These inhibitors are based on AAV-particles that present matching CAR-epitopes on their surface.

CAR-library establishment

Another task that our team is working on, is the generation of a cell based CAR-library, which will allow the rapid screening for functional, high-quality CAR-T cells against novel or personalized targets. In this project, we combine rapid large-scale transfection technology using nS/MARt vectors with single cell based selection by the use of the Berkeley Lights Lightning System. We aim on developing a pre-selection strategy based on a highly sensitive reporter cell line and FACS sorting followed by multiplexed activation analyses on the opto-electric chip of the Lightning device.

Contact: Patrick Schmidt, PhD - patrick.schmidt(at)nct-heidelberg.de

Predictive biomarker discovery

The PROMISE trial (PRedictability of Outcome based on iMmunological sIgnatureS in lung cancEr – an explorative investigation) is a collaborative exploratory biomarker study with clinical partners at the Thoraxklinik and UKHD, funded by the Dietmar-Hopp foundation. The trial focusses on the identification of predictive markers or signatures for response and resistance to current standard of care treatment in stage IV non-small cell lung cancer (NSCLC) patients. Biomaterials, such as tissue, serum, plasma, PBMCs, breath condensates and stool samples, are systematically collected longitudinally and will be analyzed by e.g. WGS/WES, PanelSeq, RNASeq, Nanostring, metagenomics, immunohistochemistry and virtual microscopy with semi-automated image analyses, multiplex Cytokine/Chemokine assays, mass spectrometry, RAMAN spectroscopy and flow cytometry.. Due to the advancement in high-throughput technologies, we incorporate heterogeneous data from multiple technologies to improve our understanding of the molecular dynamics associated with biological processes. Pipelines for multi-omics data analysis comprising MHC I/II epitope prediction and V(D)J enrichment immune profiling analysis have been set up. Further, we are developing machine- and deep learning approaches on an in-house generated graph database enabling us to extract relevant biological interpretations and to identify novel relationships by integrating high-dimensional data. For an in-depth understanding of the "individual disease" and for the identification of predictive biomarkers, an integrated analysis of the multiomics (Charoentong P et al, 2017, Cell Rep, 18(1):248-62) and wet lab data is performed.

Contact: Inka Zörnig, PhD - inka.zoernig(at)nct-heidelberg.de | Pornpimol Charoentong, PhD - pornpimol.charoentong(at)nct-heidelberg.de

Additional Projects

Our projects on ‘Tumor-host interactions in the tumor microenvironment’ and ‘Bispecific antibodies’ are conducted in close collaboration with Prof. Jäger´s Research Group Tumor Immunology (Department of Medical Oncology, UKHD). Details about this research can be found on the Tumor Immunology webpage.

Sub-Group: Targeted Tumor Vaccines

Targeted Tumor Vaccines Head: Dr. Angel Cid-Arregui

Sub-Group: Translational Research in Immuno-oncology and Microbiome (TRIM)

Translational Research in Immuno-oncology and Microbiome (TRIM) Head: Dr. Maria Paula Roberti

Team

We are a multidisciplinary team of wet-lab scientists, physicians and computational scientists.

Prof. Dr. Dirk Jäger

Group head
Dr. Marten Meyer

Deputy head, Postdoctoral researcher
Liam Bartels

Researcher
Priv. Doz. Dr. Ralf Bischoff

Postdoctoral researcher
Daniel Browne

IT system administrator
Martina Busacker-Scharpff

Technical assistant
Dr. Pornpimol Charoentong

Postdoctoral researcher, Bioinformatician
Christiane Christ

Technical assistant
Dr. Marcia Figueiredo Goncalves

Postdoctoral researcher
Isabella Gosch

Technical assistant
Monika Hexel

Technical assistant
Iris Kaiser

Technical assistant
Annette Köster

Technical assistant
Alexandra Krauthoff

Technical assistant
Claudia Luckner-Minden

Technical assistant
Dr. Yanhong Lyu

Postdoctoral researcher, Bioinformatician
Priv. Doz. Dr. Frank Momburg

Postdoctoral researcher
Dr. Alexander Rölle

Postdoctoral researcher
Dr. Patrick Schmidt

group leader transgenic T cell therapy
Dr. Lea Schweßinger

Coordinator
Selina Seith

Technical assistant
Annika Steitz

MD candidate
Claudia Tessmer

Technical assistant
Alexandra Tuch

Technical assistant
Dr. Silke Uhrig-Schmidt

Postdoctoral researcher, Equal opportunities and diversity officer
Dr. Nektarios Valous

Postdoctoral researcher
Sergio Alberto Vasquez Urbina

Researcher, Bioinformatician
Franziska Werner

PhD candidate
Katharina von Werthern

PhD candidate
Dr. Heiko Weyd

Postdoctoral researcher
Jasmin Zech

PhD candidate
Claudia Ziegelmeier

Technical assistant
Dr. Inka Zörnig

Project coordination and Lab head, Postdoctoral researcher

Entire Team

Selected Publications

2024 - Clinical and Translational Medicine

Novel chimeric antigen receptors for the effective and safe treatment of NY-BR-1 positive breast cancer

Jäger D, Berger A, Tuch A, Luckner-Minden C, Eurich R, Hlevnjak M, Schneeweiss A, Lichter P, Aulmann S, Heussel CP, Fremd C, Harbottle R, Zörnig I, Schmidt P

2024 - Frontiers in Immunology

MediMer: a versatile do-it-yourself peptide-receptive MHC class I multimer platform for tumor neoantigen-specific T cell detection

Meyer M, Parpoulas C, Barthélémy T, Becker JP, Charoentong P, Lyu Y, Börsig S, Bulbuc N, Tessmer C, Weinacht L, Ibberson D, Schmidt P, Pipkorn R, Eichmüller SB, Steinberger P, Lindner K, Poschke I, Platten M, Fröhling S, Riemer AB, Hassel JC, Roberti MP, Jäger D, Zörnig I, Momburg F

2021 - Science Advances

A nonviral, nonintegrating DNA nanovector platform for the safe, rapid, and persistent manufacture of recombinant T cells

Bozza M, De Roia A, Correia MP, Berger A, Tuch A, Schmidt A, Zörnig I, Jäger D, Schmidt P, Harbottle RP