Research Group Molecular Medicine And Immune Regulation – PD Dr. Fatih Noyan
Welcome to our research group Molecular Medicine And Immune Regulation for advanced Treg-based therapies to enhance solid organ transplant outcomes. Our research demonstrates that precisely targeted Tregs can protect transplanted organs without the debilitating side effects of conventional immunosuppression. Further, through chimeric antigen receptor (CAR) technology, we engineer Tregs to selectively neutralize donor-reactive immune cells, ensuring optimal graft acceptance.
Our ultimate goal is to integrate these innovative therapies into routine transplantation procedures in allogeneic as well as in xenogeneic organ transplantation.
Solid organ transplantation is the best treatment option for end-stage organ dysfunction. Unfortunately, the low rate of organ donation in Germany stands in stark contrast. The number of organs available for patients with end-stage organ dysfunction is not consistent with the number of organs available. Despite the advent of novel immunosuppressants, chronic organ rejection remains a challenge.
Maintenance therapy is mandatory after organ transplantations. Immunosuppressive drugs are crucial for preventing transplant rejection in solid organ recipients. Nevertheless, these pharmaceuticals have the potential to induce deleterious effects on the immune system, which may result in an increased susceptibility to infections, carcinogenesis, neoplastic diseases, metabolic disturbances (e.g., diabetes mellitus and dyslipidaemia), hypertension, and renal toxicity.
In our preclinical studies, we have successfully shown that the body needs to accept the transplanted organ, which is dependent on the therapy used to control the immune system. This approach does not interfere with the immune system and protects the transplanted organs from rejection. It is a promising and affordable way to overcome the problems of immunosuppression, its severe side effects, and the loss of quality of life in patients.
We are currently preparing to translate graft-specific Treg-based therapy into a routine clinical practice.
An alternative to organ-specific Tregs, whose antigen specificity is based on endogenous T cell receptors, is to modify the specificity of regulatory T cells.
We do this using CAR technology. CAR is a receptor that has been artificially engineered to be expressed on T cells. This allows them to spot specific antigens that are found in the transplanted organ. CAR works by joining the antigen-binding part (scFV) to the T cell signalling part via a hinge and transmembrane part. In the context of organ transplantation, CAR Tregs have been shown to recognise target antigens and accumulate at the site of action.
Owing to their regulatory capacity, CAR-Tregs facilitate local immune regulation and thus ensure the protection of the allogeneic organ from the recipient's immune cells. This new target specificity allows us to treat patients with precision without having to suppress their immune system excessively. In our preclinical studies, we showed that transferring CAR Tregs leads to organ acceptance without affecting the recipient's immune system. Our generated HLA-A*02-specific CAR Tregs approach is currently being evaluated in a phase I/II clinical trial.
Further Information
You can find the current status of our scientific publications at PubMed.
PD Dr. Fatih Noyan
noyan.fatih@mh-hannover.de
Medizinische Hochschule Hannover
Klinik für Gastroentereologie, Hepatologie, Infektiologie und Endokrinologie, OE 6815
Gebäude J11, E01, R1390
Carl-Neuberg-Str. 1
D-30625 Hannover
Telefon +49 511 532 6996
- Maike Quotschalla, M. Sc.
- Nella Redel, M. Sc.
- Andrea Schienke, VMTA
- Konstantinos Iordanidis, MTA
- Dr. Pierre Henschel
- Dr. Jakob Kremer
- Dr. Michel Tenspolde
- Dr. Katharina Zimmermann
- Dr. Louisa Ruhl
- Irina Bevzenko
- Eike Preuss
- Elvira Schulde
- Artur Wilms