Subproject 1: Virus specific T cells will be isolated based on their capacity of IFNg secretion post virus specific activation. Tacrolimus-resistant cytomegalovirus-specific T-cell products will serve as initial “blueprint“

In this research part, we will focus on the generation and characterization of anti-viral Tacrolimus-resistant T-cell products of different specificities such as cytomegalovirus/adenovirus/BK virus/Epstein Barr virus, influenza A virus and SARS-CoV-2.

All T-cell products will be functionally characterized by stimulation with viral peptide-pools and analyzed using flow cytometry. Of importance is the additional phenotypic characterization of memory T-cells that will later build the basis of our T-cell products. Virus specific T cells will be isolated based on their capacity of IFNγ secretion post virus specific activation. Tacrolimus-resistant cytomegalovirus-specific T-cell products will serve as initial “blueprint” lead product.

Finally, the feasibility of the T-cell product platform and manufacturing process will be analyzed using patient material either using samples from transplant recipients or patients suffering from virus-associated pneumonia. The final goal is the generation and characterization of multi-virus specific Tacrolimus-resistant T-cell product in order to restore the beneficial immune reaction in transplant patients.

Dr. rer. med. Michael Schmück-Henneresse, Dr. Leila Amini, Prof. Dr. med Hans-Dieter Volk

Dr. Oliver Klein

Prof. Dr. Julia Polansky-Biskup

Dr. Jacqueline Wendering

Dr. rer. nat. Stephan Schlickeiser

Dr. Mir-Farzin Mashreghi

Subproject 2: In-depth molecular characterization of Tacrolimus-resistant anti-viral TCPs and safety evaluation

In this research part, we and our cooperation partners from the Deutsches Rheuma-Forschungszentrum (DRFZ) and the Berlin Institute of Health (BIH) Core Facility “Tissue Typing” will enable in depth molecular characterization of our Tacrolimus-resistant T-cell products using single cell RNA and cellular indexing of transcriptomes and epitopes (CITE)-Sequencing technology as well as proteomics approaches. Further, amplicon sequencing will be done to evaluate potential off-target effects to re-assure patient safety during potential anti-viral T-cell Therapy.

Subproject 3: Pre-clinical in vitro testing of Tacrolimus-resistant anti-viral T-cell products with human multi-Organ-on-a-Chip models

In this research part, we and our cooperation partners from TissUse and the Translational-Immunology group of the BIH Center for Regenerative Therapies (BCRT) will perform exploratory and confirmatory proof-of-concept in vitro studies in allogenic/autologous liver/lung models with anti-viral Tacrolimus-resistant T-cell products with/without addition of Tacrolimus and other immunosuppressive drugs.

Prof. Dr. med. Hans-Dieter Volk, Dr. Anna Krebs

Prof. Dr. med. Petra Reinke, Dr. rer. nat. Andy Römhild

Dr. rer. nat. Levent Akyüz, Dr. rer. nat Kerstin Jülke

Subproject 4: Preparation of First-in-Human clinical trial for the “blueprint” product: cytomegalovirus (CMV) specific Tacrolimus-resistant T-cells

In this research part, the documentation for manufacturing authorization for severe CMV infection in transplant recipients will be achieved. In summary, the preparation of the necessary documents and all-important regulatory requirements for the patient specific therapy will be set in motion. Furthermore, technology transfer to the GMP facility, process establishment and the final validation runs for Manufacturing Authorization of the GMP process will be implemented. The technology platform will be further exploited for different virus infections and medical indications. The most promising products based on our “blueprint” product will be chosen and tested for performance. All of this will be achieved in close cooperation with the Good Manufacturing Practice (GMP) unit of the BeCAT and the immunological Study Lab (ISL) CheckImmune.

Heidi Scherm Fotografie

Firmennest - Internetagentur

Sensu - 3D animation

Cellogic

Gady Goldsobel

Subproject 1: Virus specific T cells will be isolated based on their capacity of IFNg secretion post virus specific activation. Tacrolimus-resistant cytomegalovirus-specific T-cell products will serve as initial “blueprint“

Subproject 2: In-depth molecular characterization of Tacrolimus-resistant anti-viral TCPs and safety evaluation

Subproject 3: Pre-clinical in vitro testing of Tacrolimus-resistant anti-viral T-cell products with human multi-Organ-on-a-Chip models

Subproject 4: Preparation of First-in-Human clinical trial for the “blueprint” product: cytomegalovirus (CMV) specific Tacrolimus-resistant T-cells

Subproject 5: Dissemination and Communication

Subproject 6: Exploitation of TReAT