Research Group

Immune monitoring and TCR discovery

Dr. Isabel Poschke

Teamleader

"We perform deep profiling of antigen-specific immune responses to define features of successful anti-tumor immunity in cancer patients."

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.

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. 

Publications

2024 - Nature Biotechnology
2024 - Molecular and Cellular Proteomics
2024 - Science Advances
2024 - Frontiers in Immunology
2023 - Science Translational Medicine
2023 - Nature Medicine
2023 - Neurological Research and Practice
2022 - Neuro-Oncology Advances
2022 - Neurological Research and Practice
2021 - Nature
2020 - Clinical Cancer Research

Scientist Team

4 Employees

  • Dr. Isabel Poschke

    Team Leader

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  • Dr. Katharina Lindner

    PostDoc

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  • Saskia Stange

    PhD Student

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  • Julian Hlawatsch

    MD Student

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with support of the IMU Team

Get in touch with us

Dr. Isabel Poschke
Teamleader
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