Mismatched Stem Cell Transplants Successful with Antibody Treatment

Mismatched Stem Cell Transplants Successful with Antibody Treatment

Researchers at Stanford University School of Medicine have demonstrated it is possible to transplant stem cells from a mismatched donor and avoid rejection by the immune system with an antibody treatment.

Hematopoietic stem cell transplants were first used in the treatment of certain types of cancer. Their use has now been extended to a range of autoimmune disorders.

There are two forms of treatment. One involves taking stem cells from a patient and then reintroducing them following chemotherapy, termed autologous HSCT. The other method, termed allogenic HSCT, involves obtaining stem cells from a matching donor who is usually a close relative. Finding a perfectly matched donor can be a major challenge and limits the number of patients that can receive these treatments.

While transplants are possible without a perfect match, termed a haploidentical transplant, following treatment a patient will be required to have ongoing treatment with immunosuppressive drugs to avoid rejection. If the drugs are stopped, the patient will reject the transplanted material and develop graft-versus-host disease.

Some of the problems with hematopoietic stem cell transplants can be avoided by transplanting purified hematopoietic stem cells, but the extraction and purification of the cells can be difficult.

The stem cells are usually taken from the bone marrow. After extraction, the patient undergoes chemotherapy and radiation therapy to wipe out existing stem cells and create an environment where the introduced stem cells can engraft.

Chemotherapy and radiation therapy are not without their risks. They are nonselective and can be dangerous for the patient. In fact, the potential for a patient to be harmed is so great that this form of treatment is often a last resort and only used when a patient’s life is threatened by disease.

The antibody treatment was developed to get around the need for harmful, toxic treatments and to solve the problem of having to find a near exact match donor, and to avoid the difficulties of transplanting purified hematopoietic stem cells.

The treatment involves the use of six antibodies. When the antibodies are introduced into mice, it is possible to transplant organs, tissues, blood, and stem cells that come from mismatched donors without the tissues being rejected or having to suppress the immune system with drugs.

The new antibody treatment would make it much safer for patients to undergo stem cell transplants as chemotherapy and radiation would not be required. The use of the treatment could therefore be extended to other diseases or could allow diseases to be treated earlier. It would also increase the number of suitable donors for a patient.

The antibody treatment was shown to be effective in mice. Treatment with the antibodies eliminated several different types of immune cell in the bone marrow, which allowed haploidentical hematopoietic stem cells to be introduced and engraft. The stem cells started producing blood and immune cells and there was no need to use immunosuppressive drugs.

“This finding suggests that, if these results are replicated in humans, we could have a child with sickle cell anemia in the clinic and, rather than considering stem cell transplant as a last resort and contingent on finding a perfectly matching donor, we could instead turn to transplant with stem cells from one of the child’s parents as a first-line therapy,” said George. The treatment would greatly increase the number of patients who could be provided with hematopoietic stem cell transplants).

The researchers are now embarking on a study of the antibody treatment in large animal models

The research is detailed in the paper – Antibody Conditioning Enables MHC-Mismatched Hematopoietic Stem Cell Transplants and Organ Graft Tolerance – which was published in June in the journal Cell Stem Cell. DOI: 10.1016/j.stem.2019.05.018

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