Deutsch
TU Dresden

search

Advanced Cellular Therapeutics - Anke Fuchs

Automated manufacturing of cellular therapeutics

Allogeneic hematopoietic stem cell transplantation (HSCT) is 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).

Picture: Automated manufacturing of cellular therapeutics © Anke Fuchs

Previous and current research

Establishing a novel smart Treg manufacturing protocol

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 1. 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.

Future projects and goals

The aims of our research are

  • A randomized phase II clinical trial to test smart-produced Treg cells in early chronic GvHD
  • 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

Group leader

Selected publications

Marín Morales JM, Münch N, Peter K, Freund D, Oelschlägel U, Hölig K, Böhm T, Flach AC, Keßler J, Bonifacio E, Bornhäuser M, Fuchs A. Automated Clinical Grade Expansion of Regulatory T Cells in a Fully Closed System. Front Immunol. 2019;10:38. PMID: 30778344

Fuchs A, Gliwiński M, Grageda N, Spiering R, Abbas AK, Appel S, Bacchetta R, Battaglia M, Berglund D, Blazar B, Bluestone JA, Bornhäuser M, Ten Brinke A, Brusko TM, Cools N, Cuturi MC, Geissler E, Giannoukakis N, Gołab K, Hafler DA, van Ham SM, Hester J, Hippen K, Di Ianni M, Ilic N, Isaacs J, Issa F, Iwaszkiewicz-Grześ D, Jaeckel E, Joosten I, Klatzmann D, Koenen H, van Kooten C, Korsgren O, Kretschmer K, Levings M, Marek-Trzonkowska NM, Martinez-Llordella M, Miljkovic D, Mills KHG, Miranda JP, Piccirillo CA, Putnam AL, Ritter T, Roncarolo MG, Sakaguchi S, Sánchez-Ramón S, Sawitzki B, Sofronic-Milosavljevic L, Sykes M, Tang Q, Vives-Pi M, Waldmann H, Witkowski P, Wood KJ, Gregori S, Hilkens CMU, Lombardi G, Lord P, Martinez-Caceres EM, Trzonkowski P Minimum Information about T Regulatory Cells: A Step toward Reproducibility and Standardization. Front Immunol. 2018; 15;8. PMID:29379498

Theil A,Wilhelm C, Kuhn M, Petzold A, Tuve S, Oelschlägel U, Dahl A, Bornhäuser M, Bonifacio E, Eugster A. T cell receptor repertoires after adoptive transfer of expanded allogeneic regulatory T cells. Clin Exp Immunol. 2016;187(2):316–24. PMID: 27774628

Theil A, Tuve S, Oelschlägel U, Maiwald A, Döhler D, Oßmann D, Zenkel A, Wilhelm C, Middeke JM, Shayegi N, Trautmann-Grill K, von Bonin M, Platzbecker U, Ehninger G, Bonifacio E, Bornhäuser M. Adoptive transfer of allogeneic regulatory T cells into patients with chronic graft-versus-host disease. Cytotherapy 2015;17(4):473–86. PMID: 25573333

Group members

Contact

Group Leader

Dr. Anke Fuchs

+49 (0)351 458 5642

anke.fuchs1[at]tu-dresden.de

Funding