Our immune response operates in a state of balance between defence and tolerance. Effector T cells (Teff) are responsible for immune defence, whereas regulatory T cells (Treg) regulate immune tolerance to the body itself. An imbalance towards Teff has serious consequences: the unregulated immune response attacks the body’s own cells and can destroy them, as seen, for example, in autoimmune disease.
Transplant patients receive a donated organ that is foreign to their immune system, and is recognized as being non-self. Rejection of the organ can only be prevented by massive suppression of the immune response. This comes at the price of significantly higher susceptibility to infections and even cancer.
Immunologists Dr Fatih Noyan and Dr Elmar Jäckel from the Hannover Medical School (MHH) are therefore pursuing another strategy: instead of supressing the whole immune response, they hope to generate specific immune tolerance to transplanted organs. The idea is to modify Treg cells to recognize and migrate to the donor organ, protecting it from rejection. Together with Prof. Michael Hust from the Technische Universität Braunschweig, the immunologists have developed a chimeric antigen receptor (CAR) for Treg cells specific to the antigen HLA-A*02. They have demonstrated in a model system that this approach prevents the rejection of HLA-A*02-positive organs without supressing the immune system.
‘Our hope is to be able to translate our CAR-Treg cells into everyday clinical use. The goal is to achieve a drastic reduction in the need for immunosupression after CAR-Treg cell transfer and thereby extend life expectancy for patients. The long-term survival of the transplanted organ could also be increased significantly,’ comment Dr Noyan and Dr Jäckel.
Ascenion accompanied the patent application and supported licence agreement negotiations between the MHH, TU Braunschweig and the London company Quell Therapeutics. Quell Therapeutics will develop the approach in close collaboration with the scientists and prepare and conduct clinical studies.
(Annual Review 2021/22)
