Immune monitoring and TCR discovery

Our Research

The immune monitoring unit is located at the NCT and analyzes samples from cancer patients of various entities enrolled in clinical trials. We are specialized in monitoring antigen specific adaptive immune responses and contribute to a number of phase I and phase II clinical trials in Heidelberg, across Germany, as well as to multinational trials.

In order to maximize the knowledge gained from clinical samples, our research aims to decipher characteristics of successful T cell responses that enable effective immunotherapy, or that are induced during the course of an immunological intervention. We are particularly interested to understand T cell receptor (TCR) repertoire composition and dynamics, its change during treatment and the hallmarks of T cells carrying tumor-antigen specific receptors. As part of these efforts, we work towards a warehouse of tumor-reactive TCRs, both shared- and unique-neoantigen-specific, that could be applied therapeutically.

Our projects focus on samples of patients with brain tumors, either as primary tumor site or as site of metastasis from other solid tumor entities.

This image illustrates the comparison of TCR repertoire composition for tumor responders and non-responders before and after treatment. It also shows the immune monitoring process, including the isolation and characterization of tumor-reactive TCRs from patient samples for potential use in TCR-engineered T cell therapy.

TCR Discovery Projects

We established a modular platform for the identification of tumor-specific T cell receptors (TCRs). Using epitope-specific expansion cultures (ESPEC) with subsequent identification of TCRs (SUIT) by bulk and optional single-cell TCR sequencing, we identify T cell clones with reactivity against an epitope-of-interest.

We have performed ESPEC-SUIT for >30 patients, covering hundreds of epitopes and observed robust expansion of both CD4+ as well as CD8+ T cell responses. In a sub-cohort of ten patients we selected 341 ESPEC-SUIT-derived TCRs for cloning and in vitro functional validation from >2000 candidates and confirmed antigen-reactivity for >75%.

By tracing of TCR sequences, candidate and validated antigen-specific TCRs can be mapped to other datasets, allowing us to assess for example their response to therapeutic interventions such as vaccination, and to profile their phenotype within tissue samples.

Learn more about standardized immune monitoring of clinical trials

Website of the Immune Monitoring Unit (IMU)

Publications

2025 - JITC

ESPEC-SUIT: a versatile and robust platform to identify and track antigen-specific T cell receptors in patients with cancer

Katharina Lindner, Saskia R Stange, Julian Benedikt Hlawatsch, Moritz Hamberger, Tamara Boschert, Chin Leng Tan, Ingrid Hülsmeyer, Samira Moreen Sachse, Simone Jünger, Alexander Ernst, Olga Głatki, Sofiya Vinogradova, Lena Fleischhacker, Stefan B Eichmüller, Stefan Fröhling, Jessica C Hassel, Inka Zörnig, Yanhong Lyu, Zhiqin Huang, Dirk Jäger, Frank Momburg, Marten Meyer, Lukas Bunse, Edward William Green, Michael Platten, Isabel Poschke

2024 - Nature Biotechnology

Prediction of tumor-reactive T cell receptors from scRNA-seq data for personalized T cell therapy

Tan CL, Lindner K, Boschert T, Meng Z, Rodriguez Ehrenfried A, De Roia A, Haltenhof G, Faenza A, Imperatore F, Bunse L, Lindner JM, Harbottle RP, Ratliff M, Offringa R, Poschke I, Platten M, Green EW.

2024 - Molecular and Cellular Proteomics

optiPRM: A Targeted Immunopeptidomics LC-MS Workflow With Ultra-High Sensitivity for the Detection of Mutation-Derived Tumor Neoepitopes From Limited Input Material

Salek M, Förster JD, Becker JP, Meyer M, Charoentong P, Lyu Y, Lindner K, Lotsch C, Volkmar M, Momburg F, Poschke I, Fröhling S, Schmitz M, Offringa R, Platten M, Jäger D, Zörnig I, Riemer AB

2024 - Science Advances

H3K27M neoepitope vaccination in diffuse midline glioma induces B and T cell responses across diverse HLA loci of a recovered patient

Boschert T, Kromer K, Lerner T, Lindner K, Haltenhof G, Tan CL, Jähne K, Poschke I, Bunse L, Eisele P, Grassl N, Mildenberger I, Sahm K, Platten M, Lindner JM, Green EW.

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.

2023 - Science Translational Medicine

Transcriptome-based identification of tumor-reactive and bystander CD8+ T cell receptor clonotypes in human pancreatic cancer

Meng Z, Ehrenfried AR, Tan CL, Steffens LK, Kehm H, Zenz S, Lauenstein C, Paul A, Schwab M, Förster JD, Salek M, Riemer AB, Wu H, Eckert C, Leonhardt CS, Strobel O, Volkmar M, Offringa R, Poschke I

2023 - Nature Medicine

A H3K27M-targeted vaccine in adults with diffuse midline glioma

Grassl N, Poschke I, Lindner K, Bunse L, Mildenberger I, Boschert T, Jähne K, Green EW, Hülsmeyer I, Jünger S, Kessler T, Suwala AK, Eisele P, Breckwoldt MO, Vajkoczy P, Grauer OM, Herrlinger U, Tonn JC, Denk M, Sahm F, Bendszus M, von Deimling A, Winkler F, Wick W, Platten M, Sahm K.

2023 - Neurological Research and Practice

INTERCEPT H3: a multicenter phase I peptide vaccine trial for the treatment of H3-mutated diffuse midline gliomas

Grassl N, Sahm K, Süße H, Poschke I, Bunse L, Bunse T, Boschert T, Mildenberger I, Rupp AK, Ewinger MP, Lanz LM, Denk M, Tabatabai G, Ronellenfitsch MW, Herrlinger U, Glas M, Krex D, Vajkoczy P, Wick A, Harting I, Sahm F, von Deimling A, Bendszus M, Wick W, Platten M.

2022 - Neuro-Oncology Advances

T cell receptor dynamic and transcriptional determinants of T cell expansion in glioma-infiltrating T cells

Lu KH, Michel J, Kilian M, Aslan K, Qi H, Kehl N, Jung S, Sanghvi K, Lindner K, Zhang XW, Green EW, Poschke I, Ratliff M, Bunse T, Sahm F, von Deimling A, Wick W, Platten M, Bunse L.

2022 - Neurological Research and Practice

AMPLIFY-NEOVAC: a randomized, 3-arm multicenter phase I trial to assess safety, tolerability and immunogenicity of IDH1-vac combined with an immune checkpoint inhibitor targeting programmed death-ligand 1 in isocitrate dehydrogenase 1 mutant gliomas

Bunse L, Rupp AK, Poschke I, Bunse T, Lindner K, Wick A, Blobner J, Misch M, Tabatabai G, Glas M, Schnell O, Gempt J, Denk M, Reifenberger G, Bendszus M, Wuchter P, Steinbach JP, Wick W, Platten M.

2021 - Nature

A vaccine targeting mutant IDH1 in newly diagnosed glioma

Platten M, Bunse L, Wick A, Bunse T, Le Cornet L, Harting I, Sahm F, Sanghvi K, Tan CL, Poschke I, Green E, Justesen S, Behrens GA, Breckwoldt MO, Freitag A, Rother LM, Schmitt A, Schnell O, Hense J, Misch M, Krex D, Stevanovic S, Tabatabai G, Steinbach JP, Bendszus M, von Deimling A, Schmitt M, Wick W.

2020 - Clinical Cancer Research

The Outcome of Ex Vivo TIL Expansion Is Highly Influenced by Spatial Heterogeneity of the Tumor T-Cell Repertoire and Differences in Intrinsic In Vitro Growth Capacity between T-Cell Clones

Poschke IC, Hassel JC, Rodriguez-Ehrenfried A, Lindner KAM, Heras-Murillo I, Appel LM, Lehmann J, Lövgren T, Wickström SL, Lauenstein C, Roth J, König AK, Haanen JBAG, van den Berg J, Kiessling R, Bergmann F, Flossdorf M, Strobel O, Offringa R.