Safer Allogeneic Stem Cell Transplants with Treg Therapy

A new preclinical study from the Sylvester Comprehensive Cancer Center reports that expanding regulatory T cells (Tregs) before allogeneic stem cell transplants may significantly reduce GVHD, protect vital organs, and support healthier microbiome recovery, all while preserving anti-cancer immune activity.

A New Safety Pathway for Allogeneic Stem Cell Transplants

Patients undergoing allogeneic stem cell transplants face a substantial risk of graft-versus-host disease (GVHD), which is often managed with broad-spectrum immunosuppressant drugs that increase vulnerability to infections. The new Treg-expansion strategy offers a safer, more targeted alternative by preparing the immune system before transplantation rather than suppressing it afterward.

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Treg Expansion Reduces GVHD and Protects Key Organs

Led by Robert Levy, Ph.D., researchers tested a dual-agent protocol using TL1A-Ig fusion protein and low-dose IL-2 to stimulate Tregs through TNFRSF25 and CD25 receptors. This approach expanded active Tregs into tissues frequently damaged by GVHD, including the colon, liver, and eye.

Key preclinical benefits included:

Improved survival after transplant
Reduced GVHD scores and weight loss
Stronger tissue health
More diverse, stable gut microbiome
Preservation of graft-versus-leukemia activity

The ability to lower GVHD risk without compromising anti-cancer immunity is an important finding for clinicians managing complex hematologic conditions.

Toward Practical, Patient-Centered Transplant Strategies

Unlike earlier methods that manipulate cells outside the body, this protocol expands the patient’s own Tregs internally, offering a simpler and potentially more scalable approach. The findings also highlight the impact of gut microbiome balance on transplant outcomes, an increasingly important consideration in transplant medicine.

For specialists working with allogeneic stem cell transplants, this research highlights a future where immune modulation is precise and protective rather than broadly suppressive.

The research team, spanning Sylvester, Sloan Kettering Institute, Weill Cornell, and Fred Hutchinson Cancer Center, is now working to advance this therapy toward clinical evaluation. If successful, it may help set a new standard for safer recovery, improved quality of life, and reduced complications for patients.