Transplantation with donor immune cells is often an important part of the treatment for patients with acute leukemia or other diseases of the bone marrow. The donor immune cells create a new immune system, which subsequently eliminates the patient’s leukemia cells. This helps prevent the disease
from returning. However, the risk of complications is high. The donor immune system can also mount an immune response against healthy cells and tissues. This is known as graft-versus-host disease (GvHD) and mostly affects the skin, intestines and liver. A portion of stem cell transplant patients (10– 20%) even die as a result of this condition.
GvHD arises when chemotherapy and radiotherapy damage healthy tissues. When the donor immune system responds to this damage, it can trigger an inflammatory reaction. Patients can become seriously ill from this.
Certain immune cells actually protect against tissue damage. These so-called innate lymphoid cells (ILC) are found, among other places, in the intestinal mucosa. They promote tissue repair, contribute to a healthy gut microbiome, and suppress inflammatory cells.
In our research, we have demonstrated that ILC protect against GvHD. Patients who have sufficient ILC before and after the immune cell transplant are at a significantly lower risk of developing GvHD.
That risk is reduced even further when enough ILC are present in the immune cell graft itself. A immune cell graft contains not only donor stem cells but also mature immune cells, including ILC. We have shown that the risk of GvHD is much lower when the graft contains relatively more ILC.
It is therefore essential to ensure that patients receive enough ILC from the donor during stem cell transplantation. For this reason, we have investigated how to generate mature ILC from donor stem cells. It was important in this process to use only products that are approved for clinical use in humans. Using the protocol we developed in this project, we can now grow a large number of ILC from a small quantity of donor stem cells. These cultured ILC function well.
The next step in this research is to test these cultured ILC in clinical practice. We will give stem cell transplant patients additional ILC, grown from the donor’s stem cells. The goal of this ILC therapy is to prevent the onset of GvHD and thereby improve the outcome of stem cell transplantation.