A new nano-immune therapy that programs the immune system offers hope for patients who, after an organ transplant, have to take many medications to combat rejection. A mouse study shows that targeted ‘reprogramming’ of myeloid cells successfully counteracts organ rejection without further medication. Professor Willem Mulder published these results in Immunity, the most important journal in the field of immunology. He recently started a research group at TU Eindhoven on this subject.

Patients who receive an organ transplant have to take a whole series of immunosuppressive drugs every day for life afterwards to prevent rejection of the organ. This is known as symptom control, which tries to suppress the already activated immune system. Moreover, this method has many side effects: infections and the development of cancer are no longer controlled by this paralyzed immune system. Researcher Willem Mulder and a team of internationally renowned researchers now present a nano-immunotherapy that specifically programs the right cells of the immune system in the bone marrow, even before the immune response starts. And all this while the rest of the immune system remains active.

Memory function

During an organ transplant, T-cells attack the transplanted organ and so the body rejects it. If the T cells are activated by, for example, an infection or a transplant, they ‘remember’ it. However, the T-cells are initially activated by myeloid cells. Specific treatment of myeloid cells is, therefore, an elegant way to prevent activation of the T-cell memory against the transplanted organ.

Until recently, the focus had been exclusively on suppressing the T-cells with medication, because it was thought that only these T-cells would have a memory function. The Nijmegen Spinoza premium winner Mihai Netea recently discovered that myeloid cells also have a memory function. Mulder and his team then developed a nano-immunotherapy in close collaboration with Netea to program these myeloid cells in the bone marrow. The T cells are then not activated and can still perform the normal immune response against infections and cancer.

For the study, mice were given only 3 injections with the new nano-immunotherapy within a week of a heart transplant. Without further treatment, 75% of the mice still showed no rejection symptoms after 100 days, while in all untreated mice the transplanted hearts were rejected within 10 days.

Mulder: “This technique can increase the success rate of organ transplants, making treatment safer and easier for patients. Because our nanotechnology ‘reprograms’ the immune system, we also apply this treatment strategy in other diseases in which the immune system plays an important role. We have also achieved promising results for cardiovascular disease in mouse models.”

Mulder conducted his research at the University Medical Center of Mount Sinai in New York. In February he was awarded a prestigious Vici grant of 1.5 million euros, among other things for the continuation of this research. In September he started a Precision Medicine research group at the Biomedical Technology department of Eindhoven University of Technology.

Source: TU Eindhoven