In preclinical studies, researchers found that priming the immune system with Treg expansion therapy before stem cell transplantation boosted survival, protected vital organs, and promoted a balanced gut microbiome—offering hope for safer and more effective treatment of blood cancers. The study, led by researchers at the Sylvester Comprehensive Cancer Center, part of the University of Miami Miller School of Medicine, and collaborating organizations, is highlighted on the cover of the journal’s November 27, 2025, issue. Blood.
The new protocol focuses on improving outcomes for patients undergoing allogeneic hematopoietic stem cell transplantation (aHSCT), a procedure often used to treat blood cancers and other serious conditions.
Transplant patients are at risk of developing graft-versus-host disease (GVHD), a complication where new immune cells attack the patient’s own tissues. Traditionally, doctors have used powerful drugs to suppress the immune system and prevent GVHD, but these drugs can cause side effects and leave patients vulnerable to infections.
Led by senior author Robert Levy, Ph.D., a researcher at Sylvester and professor of microbiology and immunology at the Miller School, the multi-institutional research team developed a new protocol that uses targeted immunotherapy to help the body’s regulatory T cells (Tregs) expand before transplantation. Tregs are a type of immune cell that help maintain the balance of the immune system. By increasing the number of Tregs beforehand, the body is better prepared to handle the transplant and reduce the risk of GVHD.
Our approach is to help the patient’s own immune system create a safer environment for stem cell transplantation. We’re not just suppressing the immune response—we’re directing it to key tissues involved after the transplant to promote success.”
Robert Levy, Ph.D., Sylvester Investigator and Professor of Microbiology and Immunology, University of Miami Miller School of Medicine
The researchers used preclinical models to test a combination of two agents: TL1A-Ig fusion protein and low-dose IL-2. These factors stimulate specific receptors (TNFRSF25 and CD25) on Tregs, encouraging them to proliferate and become more active. Expanded Tregs were found in key tissues such as the colon, liver, and eye areas often affected by GVHD.
The protocol led to several positive results in preclinical studies:
- Higher survival rates after transplantation
- Lower GVHD grades and less weight loss
- Better tissue health and integrity
- A more diverse and healthy gut microbiome
“We saw that expanding Tregs before transplant helped protect vital tissue organs and supported a healthier microbiome,” Levy said. “This could mean fewer complications and a better recovery for patients.”
This research is important because it offers a new way to prevent GVHD without relying solely on broad immunosuppressive drugs. By using targeted immunotherapy to expand Tregs, the protocol can reduce side effects and improve the quality of life of transplant patients.
Another key finding is that the protocol does not interfere with the body’s ability to fight cancer cells – a process known as graft-versus-graft leukemia (GVL). Maintaining GVL is crucial to prevent relapse in blood cancer patients.
“Our goal is to make transplants safer while enabling patient transplants The immune system does its job against cancer,” Levy noted. “We are working towards treatments that are effective and practical for use in the real world.”
Moving towards personalized medicine
Unlike older methods that require collecting and manipulating donor cells outside the body, Levy’s protocol works by expanding the patient’s own Tregs in vivo—inside the body—before transplantation. This approach could simplify treatment and make it more accessible.
The research also highlights the role of the gut microbiome in transplant outcomes. Patients who received the Treg expansion protocol had a more diverse and balanced microbiome, a finding that is increasingly recognized as important for immune health.
“Personalized medicine is about tailoring treatments to the needs of each patient,” Levy said. “By supporting the immune system and the microbiome, we can help patients recover more smoothly.”
He and his colleagues are working to translate these findings into clinical trials. The hope is that this protocol will become part of standard care for patients undergoing stem cell transplants, leading to fewer complications and better long-term outcomes.
“We are excited to continue this work and work with clinicians to bring new treatments to patients,” concluded Dr. Levy. “Each step forward brings us closer to safer, more effective transplants.”
Levy’s team included researchers from other leading institutions, including the Sloan Kettering Institute and Memorial Sloan Kettering in New York, Weill Cornell Medical College and the Fred Hutchinson Cancer Center in Seattle.
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