GMP & T Cell Therapy
- Immunology, Infection and Cancer
Prof. Dr. Stefan Eichmüller
head of research group
Immunotherapeutics represent promising treatment options against cancer as shown by the therapeutic success of checkpoint inhibitors. The “GMP & T cell therapy” research group explores T cell mediated tumor rejection and develops new concepts for clinical applications.
Image: Created in BioRender. https://BioRender.com/h43b574,
Our Research
Our research group investigates various possibilities for optimizing T cell-mediated tumor defense and prepares their application together with clinical cooperation partners. In our translational research, we investigate various aspects of the T cell-mediated immune response.
One important aspect is the detailed analysis of individual T cells from the tumor with regard to their ability to recognize and destroy tumor cells. The Bruker Lightning System enables such single cell analyses on a chip. Here, 1500 T cells in individual chambers of the chip are examined in parallel for their reactivity against autologous tumor cells (i.e. tumor cells from the same patient). Reactive T cells can then be exported individually from the chip to determine the genetic sequence of the reactive T cell receptor. The identified TCR gene is cloned and expressed in autologous T cells. The resulting TCR-T cells are tested for the functional recognition of autologous tumor cells. This approach is currently being used in hematological tumors (multiple myeloma) and in solid tumors such as ovarian cancer (see project “Tumor-specific TCRs”).
Solid tumours in particular are often characterized by an immunosuppressive tumour environment, which is maintained by the accumulation of suppressive cell types and inhibitory factors released by the tumour. Another project of our research group is therefore investigating miRNAs that can influence the immunosuppressive tumor environment (see project “miRNAs”).
The analysis of specific T cell responses requires synthetic peptides, which are produced in our peptide laboratory (see “Peptide Unit”). In parallel, the team of the Peptide Unit is currently establishing GMP-compliant peptide production and quality control for use in patients as part of vaccination studies.
Our GMP team is currently optimizing production lines for the manufacture of cellular products for adoptive T cell transfer. The production lines include the expansion of tumor-infiltrating lymphocytes, the production of CAR T cells and TCR transgenic T cells (see “GMP Unit”). This is done in close collaboration with Prof. Dirk Jäger's team at the NCT. A new GMP facility with cleanrooms for cell production for clinical trials is currently under construction.
Projects
Adoptive T cell transfer is currently considered the most successful treatment strategy in cancer therapy, provided that the transferred T cells recognize mutated epitopes, so-called neo-epitopes, presented by tumor cells. The major challenges of adoptive T cell therapy consitst in the definition of tumor-specific targets and the direct identification of tumor-specific T cells and their T cell receptor (TCR). In this collaborative project, we aim to directly identify myeloma-specific T cells isolated from the bone marrow of patients. Since the bone marrow aspirates contain both tumor cells and T cells, they can be used to screen for autologous, tumor-specific T cells. We use the Bruker “Lightning™ Optofluidic System”, a benchtop device that allows individual analysis of several thousand cells in separate nanopins on a chip. The functional interaction between sorted myeloma cells and individual T cells is analyzed by quantifying the cytokines released by reactive T cells. In a next step, the T cells identified in this way are isolated from the chip for TCR sequencing and DNA vectors are generated that code for the identified TCRs. Finally, the tumor reactivity of these TCRs against the autologous myeloma cells is tested. Ultimately, such strategies could be used to generate autologous TCR-transgenic T cells for the adoptive T cell therapy of patients with multiple myeloma. Meanwhile we have extended the application of the Bruker “Lightning™ Optofluidic System” to solid tumors such as ovarian and colorectal cancer.
Production of CAR-T cells
Cleanroom Production
Prof. Dr. Stefan Eichmüller
You can find Prof. Eichmüller's CV below as PDF download.
Team
Team GMP & T cell therapy
Our working group consists of different sub-units: a scientific working group and a GMP unit, which are currently located in the main building, as well as a peptide unit in building TP4 of the Technology Park.
For more information please follow the link “Entire team” below.
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Prof. Dr. Stefan Eichmüller
head of research group
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Dr. Yannic Altrichter
project manager peptide production
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Felix Andres
PhD student
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Kai Beißer
technician peptides
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Chantal Crocoll
B.Sc. peptides
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Elke Dickes
technician research, GMP
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Sabrina Kempf
technician GMP
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Dr. Bettina Meißburger
project manager GMP, cell therapy
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Robin Mölle
technician peptides
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Dr. Wolfram Osen
group leader preclinical research
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Dr. Constanze Paulus
Postdoc, quality control peptides
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Rainer Schell
technician GMP
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Dr. Patrick Schmidt
group leader transgenic T cell therapy
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Fabian Sieker
master student
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Claudia Sterzik-Luksch
technician GMP
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Julian Thimm
project manager GMP compliance
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