For lymphoma, leukemia and other hard to treat blood cancers, stem cell transplant most efficient method. The process involves replacing patient’s blood-forming stem cells with donor’s stem cells. Therefore, destroying cancer cells in blood, lymph nodes and bone marrow. Hence, researchers have found a new method to safer stem cell transplant for blood cancer.
Many patients with blood cancer are weak to bear stem cell transplant. That is because patients stem cells needs to be destroyed first, with chemotherapy. Similarly, at times total body radiation is needed before adding donor’s stem cells. This way makes room for the donor stem cells. It helps to remove remaining cancer cells in the body. It decreases patient’s immune system so it will not attack donor’s stem cells. However, toxicity and suppression of immune system produced by these, puts patient at high risk of organ damage, infection and other side effects.
Stem cell transplant for blood cancer
Researchers at Washington University School of Medicine, while studying mice have developed a new method of safer stem cell transplant that do not need radiation or chemotherapy. John F. DiPersio, MD, Ph.D. E. & Sam J. Golman, Professor of Medicine, believes, ” To be able to do a stem cell transplant without having to give radiation or chemotherapy would be life-changing.” Instead, the process uses an immunotherapeutic approach.
To stop rejection by immune system to new donor cells, blood-forming stem cells that are to be removed, are combined with immune-modulating drugs. Stem cell transplantation was successful in mice. By using unrelated mice without proof of dangerously low blood cell counts that are signs of common procedure. Therefore, this research promotes safer stem cell transplant. It means cure for patients with different type of blood cancer. It can also be use to treat disease like sickle cell anemia or other genetic disorders that are less fatal.
Preventing immune system rejection
Instead of using high dose chemotherapy and full body radiation, DiPersio and his team made drugs that are toxic to cells. Attach to these drugs were the antibodies that attack specific surface protein expressed on bone marrow stem cells. These antibody drug conjugate (ADC) attach to those specific proteins and then internalized by stem cell, eventually causing cell death. Scientist created 2 different ADCs to target 2 specific protein, hence reducing damage to other types of cells.
Researchers treated mice with immunosuppressive compounds called Janus kinase (JAK) inhibitors to prevent immune system rejecting donor cells. Therefore, they used baricitinib, FDA approved drug to treat arthritis. “By combining the antibody-drug conjugates with JAK inhibitors, we were able to achieve a successful transplant between two individual strains of mice,” said Stephen P. Persaud, MD, Ph.D., an instructor in pathology & immunology.
According to the researchers, the new method struck balance between donor immune cells attacking leukemia cells (graft-versus-leukemia effect) in mouse model of leukemia and not attacking receivers healthy tissue (graft-versus-host disease). Whereas, mice in this study did not develop graft-vs-host disease because of immune suppressing drugs. This also proved to be a plus point for this technique.
“When you give JAK inhibitors from the beginning, there is evidence that they prevent graft-versus-host disease from developing later,” said DiPersio. ” Chemotherapy and radiation destroy all the old cells at once. With the new strategy, the old cells were slowly replaced by donor cells, and so we never saw any drop in the blood cell counts in these mice. The blood cell counts looked normal the whole way, and in the end, we could see that all the blood cells originated from the new donor cells.”
After sometime, investigators found that they could slowly decrease JAK inhibitors. Once the donor stem cells have completely replaced the original cells. Hence, stopping the immune suppression fully.
“We’ve shown that we can use this relatively simple regimen that is minimally toxic to transplant donor stem cells across immunologic barriers in mice,” Persaud said. “We need more research to see if the same strategy will be suitable to humans. We are working to improve the technique in mice. Then we will likely test it in other animal models of leukemia before. We would begin planning a clinical trial to investigate the strategy in patients.”