Regulatory T cells (Tregs) in xenotransplantation (A04)

• Subject Area: Immunology ; Gastroenterology
• Term: from 2012 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 213602983

We successfully generated and characterised a chimeric antigen receptor (CAR) for Treg modulation that specifically identifies porcine target structures. CAR-modulated Tregs were then able to protect xenogeneic grafts. In the upcoming funding period, we will characterise and optimise the clinical applicability of our Xeno-CAR-Treg products. This includes stabilisation of the Treg phenotype after CAR modulation by ectopic FOXP3 expression. In addition, we will improve on the properties of the CAR-Tregs. To fill the created immunologic niche and in order to maintain a large number of CAR-Tregs in the recipient organism, Treg-optimising inducible promoters will be used, Treg-specific or immunomodulating cytokines. This should lead to an advantage in terms of CAR-Treg viability, their cell number and suppressivity and finally their clinical effectiveness. With regard to translation, we will first optimise our Xeno-CAR-Tregs after transplantation of porcine islet cells in the humanised mouse model. Thereafter, we will test the effectiveness of our Xeno-CAR-Tregs in the preclinical NHP model.

• DFG Programme: CRC/Transregios
• Subproject of: TRR 127: Biology of Xenogeneic Cell and Organ Transplantation - From Bench to Bedside
• Applicant Institution: Ludwig-Maximilians-Universität München
• Project Heads: Professor Dr. Elmar Jaeckel; Privatdozent Dr. Fatih Noyan; Dr. Heike Pohla, until 6/2015