Researchers develop new strategy to limit side effects of stem cell transplants

August 15, 2016, Rockefeller University Press
Fluorescence microscopy of mouse lymph nodes reveals that treatment with STAR2 (right) increases the number of regulatory T cells, which express a protein called Foxp3 (red). Credit: Chopra et al., 2016

Scientists in Germany have developed a new approach that may prevent leukemia and lymphoma patients from developing graft-versus-host disease (GvHD) after therapeutic bone marrow transplants. The researchers describe the successful application of their strategy in mice in "Exogenous TNFR2 activation protects from acute GvHD via host T reg cell expansion," which will be published online August 15 ahead of issue in The Journal of Experimental Medicine.

Bone marrow transplants can cure types of leukemia and lymphoma because derived from the donor's bone marrow can develop into immune cells capable of killing the patient's . But the donor-derived immune cells may also attack the transplant recipient's healthy tissues, producing the diverse and sometimes severe symptoms of GvHD. One approach to avoiding GvHD is to co-transplant large numbers of regulatory T cells (T reg cells), that can suppress the donor cells' effects on healthy tissue while maintaining their ability to kill tumor cells. This approach is challenging, however, because the T reg cells must first be isolated from the donor's peripheral blood or bone marrow and then cultivated in the laboratory to produce sufficient numbers for transplantation.

A team of researchers led by Andreas Beilhack and Harald Wajant of the University Hospital W?rzburg devised an alternative way to prevent GvHD in mice, developing a protein called STAR2 that can stimulate the formation of the transplant recipient's own T reg cells in vivo. Pretreating mice with STAR2 protected them from developing GvHD after immune cell transplantation. The donor-derived cells retained their ability to kill the recipient's lymphoma cells, however.

STAR2 works by specifically binding to a cell surface protein called TNFR2, activating a signaling pathway that increases the number of T reg cells. Beilhack and colleagues found that a slightly modified version of STAR2 has a similar effect on human T reg cells, suggesting that the approach could also prevent GvHD in leukemia and lymphoma patients after or hematopoietic stem cell transplants. "Furthermore, this strategy may be beneficial for other pathological settings in which elevated numbers of regulatory T cells are desirable, such as autoimmune diseases and solid organ transplantation," Beilhack says.

Explore further: Immune cell subset is associated with development of gastrointestinal GVHD after HSCT

More information: Chopra, M., et al. 2016. J. Exp. Med. DOI: 10.1084/jem.20151563

Related Stories

Immune cell subset is associated with development of gastrointestinal GVHD after HSCT

May 5, 2016
Gastrointestinal graft vs. host disease (GI-GVHD) is a life threatening complication that can occur after allogeneic hematopoietic cell transplantation, a procedure that is commonly used to treat patients with leukemia. There ...

Depletion of naive T cells from stem cell grafts limits chronic graft-versus host disease

June 8, 2015
Stem cell transplantation is used to treat hematologic malignancies, such as leukemia. Patients that receive donor cells are at risk of developing graft-versus host disease (GVHD). This potentially fatal complication results ...

Less toxic bone marrow transplants on horizon

August 10, 2016
Bone marrow transplants that do not require dangerous and often toxic chemotherapy could soon be possible, US researchers said Wednesday after seeing initial success with experiments on mice.

No survival advantage with peripheral blood stem cells versus bone marrow

October 19, 2012
(Medical Xpress)—Claudio Anasetti, M.D., chair of the Department of Blood & Marrow Transplant at Moffitt Cancer Center, and colleagues from 47 research sites in the Blood and Marrow Transplant Clinical Trials Network conducted ...

Immune cells found to prevent bone marrow transplant rejection

June 27, 2014
(Medical Xpress)—Cornell researchers have identified a type of immune system cell that prevents a patient's body from attacking donor cells after a bone marrow transplant, a condition called graft-versus-host disease (GVHD).

Immunotherapy benefits relapsed stem cell transplant recipients

July 13, 2016
For many patients with advanced blood cancers, a stem-cell transplant can drive the disease into remission. However, about one-third of these patients experience a relapse and face a very poor prognosis.

Recommended for you

LincRNAs identified in human fat tissue

June 21, 2018
A large team of researchers from the U.S. and China has succeeded in identifying a number of RNA fragments found in human fat tissue. In their paper published in the journal Science Translational Medicine the group describes ...

Scientists solve the case of the missing subplate, with wide implications for brain science

June 21, 2018
The disappearance of an entire brain region should be cause for concern. Yet, for decades scientists have calmly maintained that one brain area, the subplate, simply vanishes during the course of human development. Recently, ...

Key molecule of aging discovered

June 21, 2018
Every cell and every organism ages sooner or later. But why is this so? Scientists at the German Cancer Research Center in Heidelberg have now discovered for the first time a protein that represents a central switching point ...

Compound made inside human body stops viruses from replicating

June 20, 2018
The newest antiviral drugs could take advantage of a compound made not by humans, but inside them. A team of researchers has identified the mode of action of viperin, a naturally occurring enzyme in humans and other mammals ...

Research reveals zero proof probiotics can ease your anxiety

June 20, 2018
If you're expecting probiotics to reduce your anxiety, it might be time to put down that yogurt spoon—or supplement bottle—and call a professional instead.

Long-term estrogen therapy changes microbial activity in the gut, study finds

June 20, 2018
Long-term therapy with estrogen and bazedoxifene alters the microbial composition and activity in the gut, affecting how estrogen is metabolized, a new study in mice found.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.