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Education for tolerance

Researchers from the Weizmann Institute have developed a new method to create "immune tolerance" which may facilitate transplants, and even promote medical treatments using living cells

Laboratory flasks containing thousands of white blood cells from a patient who developed "immune tolerance" to the donor after a bone marrow transplant. The cells show no signs of rejection of the donor cells (three columns on the left), but secrete chemicals that indicate rejection (indicated in red) when exposed to the cells of a third person (three columns on the right). Source: Weizmann Institute magazine.
Laboratory vials containing thousands of white blood cells from a patient who developed "immune tolerance" to the donor after a bone marrow transplant. The cells show no signs of rejection of the donor cells (three columns on the left), but secrete chemicals that indicate rejection (indicated in red) when exposed to the cells of a third person (three columns on the right). Source: Weizmann Institute magazine.

The lives of thousands of patients with leukemia and other malignant blood diseases are saved thanks to bone marrow transplants that are performed without a complete match between patient and donor. However, these transplants are dangerous, as it is necessary to suppress the patient's immune system before the transplant so that his body does not reject the incompatible cells. Because of this, the patient is more vulnerable to infections. In a new study, which Recently published in the scientific journal Blood advancesSucceeded Prof. Yair Reisner and his group in the immunology department of the Weizmann Institute, together with colleagues in Italy, to significantly reduce the need to suppress the immune system before and after transplants where there is no match between donor and recipient. The new method may not only make bone marrow transplants safer, but also facilitate organ transplants and promote medical treatments using living cells.

The study is based on Previous work of Prof. Reisner, who more than two decades ago developed a method for bone marrow transplantation without a complete match between patient and donor - using huge doses of bone marrow cells that help the transplanted cells overcome rejection. The opposite problem, i.e. a situation where the transplanted tissue attacks the host body, is prevented by "cleansing" the bone marrow of the main "suspects" of aggression: the T cells of the immune system.

In order to reduce the need to suppress the immune system, Dr. Ester Bacher-Lustig and the other members of Prof. Reisner's group, together with doctors from Italy, have now combined the giant-dose approach of bone marrow cells with an approach that has so far been applied in other circumstances: chemotherapy drug treatment cyclophosphamide (PTCY) shortly after transplantation. "This drug kills dividing cells, and after the transplant, the cells that divide rapidly are the patient's T cells, which 'raise their heads' after recognizing foreign tissue," says Prof. Reisner. "However, since the drug does not kill cells that are not dividing, it also does not harm the other components of the immune system."

If the combined method proves itself in trials in a larger number of patients, it may allow organ transplants, such as a kidney or liver, without the need for dangerous suppression of the immune system. The method may also help treat cancer patients using cells of the immune system taken from the person who donated the cells to the bone marrow

Prof. Yair Reisner and Dr. Esther Bacher-Lustig. Immune tolerance - the highlight of the transplant field. Source: Weizmann Institute magazine.
Prof. Yair Reisner and Dr. Esther Bacher-Lustig. Immune tolerance - the highlight of the transplant field. Source: Weizmann Institute magazine.

In a study conducted on mice, Prof. Reisner and his group showed that large doses of bone marrow cells in combination with cyclophosphamide created a condition known as "immune tolerance". This is the highlight of the field of transplants, and the state we strive to reach when treating patients - the patient's immune system does not reject the donor's cells and tissues. The bodies of the mice treated with the combined method became so "tolerant" that after the bone marrow transplant, their bodies did not reject skin grafts from the same donor, even though they did not receive drugs to suppress the immune system.

Following the success of the experiment in mice, Prof. Franco Abarza and his colleagues at the University of Parma in Italy using the combined method in three blood cancer patients - two with multiple myeloma and one with Hodgkin's lymphoma - who underwent bone marrow transplants from mismatched donors. In two of the patients, the tissue was absorbed quickly, even though they were treated with radiotherapy at a dose that was tens of percent lower than the standard dose; In the third patient, it was absorbed into the bone marrow only after normal dose radiation. One way or another, in all three cases the disease disappeared. Later, tests revealed that the two who were treated with low-dose radiation demonstrated "immune tolerance" towards the donor.

If the combined method proves itself in trials with a larger number of patients, it may allow organ transplants, such as a kidney or liver, without the need for dangerous suppression of the immune system - as long as the source of the transplanted organ is from a person who also donated the huge dose of bone marrow cells. The method may also help treat cancer patients using cells of the immune system taken from the person who donated the cells to the bone marrow.

In addition, since the combined method is safer, it may allow bone marrow transplants in elderly patients who are unable to withstand the immunosuppression required today. Also, the method may allow transplants from a donor to a recipient who are not compatible, for the treatment of blood diseases such as sickle cell anemia, thalassemia and autoimmune diseases, which are not immediately life-threatening, and therefore do not justify the use of dangerous treatments.

Prof. Reisner's group also included Dr. Noga Or-Geva and Dr. Yael Zlotnikov-Klionsky. Besides the University of Parma, the collaboration with the Italian Academy also included doctors from the University of Perugia and the University of Modena.

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