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Stanford University researchers say antibody-based therapy can effectively eliminate stem cells from blood cells



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According to a study in mice, the researchers believe that treatment can bypass the need to use chemotherapy or severe, life-threatening radiation to prepare people for transplantation, which greatly increases the number of people who can benefit from the procedure.

Antibody-based therapy can subtly and efficiently reduce stem cells formed in the blood in the bone marrow to prepare for healthy stem cell transplantation, according to a study in mice by researchers at the Stanford University School of Medicine.

The researchers believe the treatment could bypass the need to use chemotherapy or severe, life-threatening radiation to prepare people for transplantation, which greatly increases the number of people who can benefit from the procedure.

"There are a lot of blood disorders and immune diseases that can be cured by transplanting healthy stem cells," says Judith Shizuru, a doctorate of medicine at Stanford University. "But the pre-treatments needed to get the healthy cells to transplant effectively are so toxic that we can not offer this option to many patients. The treatment that targets only specific blood-producing stem cells will allow us to potentially cure people with diseases as diverse as sickle cell disease, Thalassemia, autoimmune disorders, and other blood disorders. "

Shizuru is the senior author of the study, which was published online on February 11 at blood. Postdoctoral researcher Wendy Fang, MD, Doctor of Philosophy, and Professor of Pediatrics Agnieszka, MD, PhD, shares the lead author of the work.

The study is one of two recently co-authored by Shizuru, and research researcher Hi-suk Kwon, PhD, indicating that antibodies directed to a protein called CD117 on the blood cells or hematopoietes can be effective and safe to eliminate Cells in mice and non-human items. CD117 is a protein found on the surface of stem cells. It regulates growth and activity; The antibody, called SR1, binds to protein and prevents its function.

The use of antibodies against CD117 to prevent stem cells forming blood is based on studies conducted in the laboratory of research author and author Irving Weissman, MD, Stanford Director of the Institute of Stem Cell Biology and Regenerative Medicine of the Center for Stem Cell Cancer Research and Medicine at Stanford University, and by graduate student In & quot; Covici & # 39;

The results of these studies, including an article recently published in blood Written by Kwon who showed that antibody therapy is safe in non-human barites, set the stage for a clinical trial of the Stanford antibody and at the University of California at San Francisco for children with an immune disorder called severe combined depression.

Hematopoietic stem cells are found in the bone marrow. They raise all blood cells and the immune system. Leukemia, such as leukemia, arises when stem cells or their offspring begin to divide uncontrollably; Other genetic conditions such as sickle cell anemia or thalassemia occur when hematopoietic stem cells produce red blood cells or hemoglobin.

Often the best chance for a cure for these and other diseases originating from the bone marrow is to eliminate the damaged hematopoietic stem cells from the patient and replace them with healthy stem cells from a closely matched donor. But in order to do so, the patient must be able to withstand a pre-treatment, known as conditioning. Most conditioning systems consist of a combination of chemotherapy and radiation at doses high enough to kill stem cells in the brain.

Shizuru and her colleagues have learned a mouse model of a class of human diseases called myelodysplastic syndrome, or MDS. People with MDS are unable to produce mature and functioning blood cells, and the only drug is stem cell transplantation. The disease mainly affects older people, who are more likely than younger people to have more, complicated medical factors, who are less likely to resist conditioning regimen.

"Many of these people are elderly and unable to qualify for a transplant," Fang said. "But there is no other cure for MDS."

Because there are different types of MDS, patients receive risk levels based on the type of disease, blood test results, presence or absence of specific mutations in the affected cells. According to the World Health Organization, patients with low risk MDS have a median survival rate of 5.5 years; Those with high-risk disease have a median survival of 2.2 years.

SR1, an antibody antibody CD117 and covet, identifies CD117 on hematopoietic stem cells isolated from healthy donors or patients with MDS. They found that the antibody blocked the growth of both healthy and diseased stem cells in the laboratory. Subsequently, the researchers investigated the effect of SR1 treatment on mice that were designed to be a hybrid blood system consisting of both human and mouse hematopoietic stem cells.

They found the mice that SR1 quickly and efficiently eliminated both healthy human and hematopoietic stem cell cells isolated from low-risk MDS disease. In these animals with diseased human stem cells, SR1 significantly improved the ability of healthy hematopoietic stem cells to transplanted after implantation.

"SR1 is directed directly at cells that activate diseases for the purpose of eliminating mice, although these cells generally have a significant competitive advantage," Fang said. "This is the first antibody directed against CD117, which has been shown to clear the normal human cells and patients from the recipient, and we are very pleased with the results."

Although SR1 is also able to significantly reduce the number of high-risk MDS cells from mice, the researchers found that the effect was transient: patient cells eventually returned even after implantation. In such cases, it may be necessary to combine treatment with CD117 with other treatments to completely eliminate the diseased cells, the researchers believe.

"Based on the results of this study and others, we received approval from the US Food and Drug Administration to proceed with a clinical trial for MDS patients using a version of SR1 suitable for human trials," Shizuru said. "We very much hope that this body of research will have a positive effect on patients by providing better depletion of patients' cells and engraftment of healthy cells."

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