Aims

The newly established immuno-oncology platform will use the innovative cell type-specific gene transfer technologies available at FCI to develop new immunotherapeutic concepts. These include the genetic modification of T lymphocytes or natural killer cells (NKs) with chimeric antigen receptors (CARs) as well as the precise transfer of immunomodulatory agents into tumor tissue.

The necessary vector systems have been and are being developed within the FCI by the partner PEI. World-leading in the generation of so-called receptor-targeted vectors, CD4- and CD8-targeted lentiviral vectors have been generated, which can introduce therapeutic genes highly selectively with more than 99% precision into the respective subtypes of T-lymphocytes. This precise gene transfer not only works ex vivo in cultured cells, but also in vivo, in mouse models, the general feasibility of the concept could be demonstrated. Thus, proof-of-concept for in vivo generation of CAR-T cells was achieved using such vectors. The application of these vectors to new therapeutic strategies as well as the transfer of the vector engineering concept to AAV vectors and lipid nanoparticles are the focus of ongoing activities. This also concerns the analysis of interactions between tumor cells and immune cells, which are often crucial for the successful treatment of cancer. These will be investigated at all levels from transcription to proteome and up to cell-cell interactions and will be presented as an overall picture. In addition, the spatial interaction between immune and tumor cells will be in the focus.

Resources

The Paul Ehrlich Institute has the infrastructure to generate lentiviral vectors and AAV vectors for preclinical applications in animal models. With the recent acquisition of nanoassemblers (Spark and Ignite), RNA lipid nanoparticles (LNPs) for ex vivo and in vivo applications can now also be generated at different scales and used for applications in FCI.
Immunomonitoring resources are described separately, including the infrastructure available for transcriptome analyses in tumor tissue.

Possible future scenario for in vivo CAR T cell generation. Shown on the left is infusion of T cell-specific vector particles (lentiviral, AAV, or lipid nanoparticles) and on the right is selective gene transfer into T cells in patient blood vessels. Modified after Michels, Ho & Buchholz (2022) Molecular Therapy 30, 2401.

People

Technology Platform 2 Immuno-oncology is headed by Christian Buchholz.
This area will be significantly strengthened by the newly recruited W2 professorship and a junior research group for tumor immunology, which will establish a new technology focus in this field.
For the immunomonitoring platform (headed by Karl H. Plate) of the FCI projects, an additional Staff Scientist was recruited. A doctoral researcher is working on vector engineering.

The following scientists participate in Technology Platform 2:

W2-Tumor Immunology

W2 Professur

Leitung:Christian Buchholz

  • Christian Buchholz
  • Bernhard Brüne
  • Katharina Imkeller
  • Karl H. Plate
  • Yvonne Reiss
  • Michael Rieger
  • Evelyn Ullrich
  • Mélanie Tichet
  • Andreas Weigert
  • Staff Scientist: Jonathan Schupp