Through experimental work, an international team of researchers directed by City of Hope’s Defu Zeng, professor of diabetes immunology and hematopoietic cell transplantation, believe they may have discovered a way to prevent graft-versus-host disease after stem cell transplants while retaining the transplants’ positive effects on fighting leukemia and lymphoma. The preclinical study results were published within the Journal of Clinical Investigation .
Allogeneic (meaning from a donor) hematopoietic cell transplantation (HCT) is a curative therapy for malignancies of the blood and lymph system, including leukemia plus lymphoma. It works by introducing healthy immune cells, or even T cells, that eliminate tumor cells and prevent the particular cancer from relapsing. Unfortunately, the same donor T tissue can also attack the healthy tissue of the recipient’s entire body such as gut, liver, lung, and skin, leading to induction of graft- (T cell) versus-host (recipient’s body) condition, or GVHD. Symptoms can be mild to severe and sometimes include mouth ulcers, gastrointestinal distress, and rashes.
“Currently, immunosuppressive drugs have been used to prevent GVHD, but immune-suppressants also subdue the anti-cancer effects of the particular donor T cells, potentially resulting in cancer relapse, along with other side effects such as an increased risk of infection, inch explains Zeng. “Therefore, prevention of GVHD while conserving anti-cancer effects remains the ‘holy grail’ of allogenic HCT. ”
According to the paper, titled “PD-L1 interacts with CD80 to regulate graft-versus-leukemia activity of donor CD8+ T cells, ” the research team, which included graduate learners (first authors Qingxiao Song and Xiong Ni) plus scientists from City of Hope, Mayo Clinic, Fred Hutchinson Cancer Research Center and three Chinese medical colleges, observed that temporary in vivo depletion of a particular type of donor T cells (CD4+) soon after infusion associated with donor stem cell transplants prevented GVHD while conserving strong graft-versus-leukemia (GVL) effects.
The exhaustion of CD4+ cells essentially caused another type of T cellular (CD8+) to become exhausted in their quest to destroy regular tissue, but strengthened in their fight against cancer, meaning that the particular donor CD8+ T cells eliminated tumor cells with no causing GVHD.
“If successfully translated directly into clinical application, this regimen may represent one of the new approaches that allow strong GVL effects without leading to GVHD, ” says Zeng. “This kind of regimen has got the potential to promote wide-spread application of allogenic HCT as a healing therapy for hematological malignancies. ”
In the years ahead, Zeng plans to translate this novel regimen in to clinical application at City of Hope by carrying out a medical trial in collaboration with Ryotaro Nakamura, M. M., associate professor of hematology and hematopoietic cell hair transplant, and Stephen J. Forman, M. D., F. The. C. P, the Francis & Kathleen McNamara Recognized Chair in Hematology and Hematopoietic Cell Transplantation plus leader of City of Hope’s Hematologic Malignancies and Originate Cell Transplantation Institute, which is one of the world’s largest and many successful bone marrow and blood stem cell hair transplant centers.
“If we see promising outcomes, we will extend this trial by working with our collaborators from this current study, ” says Zeng.
Materials provided by City of Wish . Note: Content may be edited to get style and length.