Development of Advanced Cellular Therapeutics
Previous and Current Research
The development of personalized cellular therapy has been one of the major breakthroughs of the last decade. The Fuchs lab is especially interested in the clinical translation of cell therapy in the context of autoimmune disease and allogeneic hematopoietic stem cell transplantation (HSCT) as a potentially curative treatment for life-threatening hematopoietic disorders such as leukemia and lymphoma. However, despite improved conditioning regimens, graft-versus-host disease (GvHD) – an attack of patient tissue by immune cells within the graft -remains a major complication affecting every second transplanted patient. Frequent resistance to current treatment options makes GvHD the leading cause of premature non-relapse mortality in HSC recipients followed by infection. Our group develops novel individualized cell-based therapeutics to combat the unmet clinical need for efficient treatment of GvHD and viral infection after HSCT. We work in close collaboration with the Good Manufacturing Practice (GMP) facility of the Center for Regenerative Therapies Dresden (CRTD).
Current research of our group shows that re-balancing tolerance in the new immune-system with an additional dose of stem cell donor-derived immune cells (Regulatory T cells, “Tregs”) can alleviate chronic GvHD-complications after transplantation. Generating this advanced therapy medicinal product (ATMP) is laborious and involves a second blood cell donation (“apheresis”), isolation and expansion of the cells under “Good Manufacturing practice (GMP)” conditions. Recently our group established a novel smart Treg manufacturing protocol based on an automated closed system that simplifies this procedure. Furthermore, we have an ongoing collaboration with the lab of Prof. Michael Bachmann for upscaling and GMP translation of antigen-directed Treg generated by advanced chimeric antigen receptor (CAR) based approaches. In a second project, we are currently establishing the fully automated isolation of virus-specific T cells in collaboration with the local adult and pediatric HSCT centers.
In addition, we are developing immunomonitoring pipelines to track infused cells including T cell receptor sequencing and to monitor changes in cellular and soluble markers post cell transfer.
The Fuchs lab welcomes students with a strong interest in clinical translation and GMP, aiming at a career in clinical immunology and/or cell therapy in academia, patient care or industry.
Future Projects and Goals
- A randomized phase II clinical trial to test smart-produced Treg cells in early chronic GvHD
- Clinical translation of antigen-targeted Treg
- Automated GMP production of antigen-specific T cells to treat viral infections in immune-compromised patients
- Adaptation of the smart manufacturing strategy to other immune cells used in cancer therapies
- Deep immunomonitoring of patients including flow- and mass cytometry (CyTOF), T cell receptor sequencing and single cell and RNA sequencing
Methodological and Technical Expertise
- Cell culture
- Flow and mass cytometry
- T cell receptor and RNA sequencing
- Good Manufacturing Practice (Clean room grade A, B, C)
- clinical grade cell isolation and expansion
Anke Fuchs, née Theil
Marín Morales JM, …, Fuchs A
Automated Clinical Grade Expansion of Regulatory T Cells in a Fully Closed System.
Front. Immunol. 10, 38 (2019)
Fuchs A et al
Minimum information about T regulatory cells: A step toward reproducibility and standardization.
Front. Immunol. 8, 1–15 (2018)
Theil A et al
T cell receptor repertoires after adoptive transfer of expanded allogeneic regulatory T cells.
Clin. Exp. Immunol. 187, 316–324 (2016)
Theil A et al
The relative merits of cord blood as a cell source for autologous T regulatory cell therapy in type 1 diabetes.
Horm Metab Res 47, 48–55 (2015)
Theil A et al
Adoptive transfer of allogeneic regulatory T cells into patients with chronic graft-versus-host disease.
Cytotherapy 17, 473–486 (2015)