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A treatment strategy that increases the production of regulatory T cells (Tregs) can prevent graft-versus-host disease (GVHD) in mice, according to research published in The Journal of Experimental Medicine.
One way to prevent GVHD after allogeneic hematopoietic stem cell transplant (allo-HSCT) is to co-transplant large numbers of Tregs, which can suppress the donor cells’ effects on healthy tissue without affecting their ability to kill tumor cells.
This approach is challenging, however, because the Tregs must first be isolated from the donor’s peripheral blood or bone marrow and then cultivated in the lab to produce sufficient numbers for transplant.
Andreas Beilhack, MD, of University Hospital Würzburg in Germany, and his colleagues have found a way to overcome this obstacle, at least in mice.
The team developed a protein agonist called STAR2, which selectively activates TNFR2. The researchers noted that TNF and its receptors, TNFR1 and TNFR2, have been shown to play a crucial role in both GVHD and the graft-versus-leukemia effect.
With their experiments, Dr Beilhack and his colleagues showed that STAR2 binds to TNFR2, activating a signaling pathway that increases the number of natural Tregs in vitro and in vivo.
The team also tested STAR2 in mice with lymphoma. Pretreating the mice with STAR2 protected them from developing GVHD after allo-HSCT. And the donor-derived cells retained their ability to kill lymphoma cells.
In addition, the researchers found that a slightly modified version of STAR2 has a similar effect on human Tregs, which suggests this approach could also prevent GVHD in humans undergoing allo-HSCT.
“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,” Dr Beilhack said. 
Photo by Aaron Logan
A treatment strategy that increases the production of regulatory T cells (Tregs) can prevent graft-versus-host disease (GVHD) in mice, according to research published in The Journal of Experimental Medicine.
One way to prevent GVHD after allogeneic hematopoietic stem cell transplant (allo-HSCT) is to co-transplant large numbers of Tregs, which can suppress the donor cells’ effects on healthy tissue without affecting their ability to kill tumor cells.
This approach is challenging, however, because the Tregs must first be isolated from the donor’s peripheral blood or bone marrow and then cultivated in the lab to produce sufficient numbers for transplant.
Andreas Beilhack, MD, of University Hospital Würzburg in Germany, and his colleagues have found a way to overcome this obstacle, at least in mice.
The team developed a protein agonist called STAR2, which selectively activates TNFR2. The researchers noted that TNF and its receptors, TNFR1 and TNFR2, have been shown to play a crucial role in both GVHD and the graft-versus-leukemia effect.
With their experiments, Dr Beilhack and his colleagues showed that STAR2 binds to TNFR2, activating a signaling pathway that increases the number of natural Tregs in vitro and in vivo.
The team also tested STAR2 in mice with lymphoma. Pretreating the mice with STAR2 protected them from developing GVHD after allo-HSCT. And the donor-derived cells retained their ability to kill lymphoma cells.
In addition, the researchers found that a slightly modified version of STAR2 has a similar effect on human Tregs, which suggests this approach could also prevent GVHD in humans undergoing allo-HSCT.
“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,” Dr Beilhack said.
Photo by Aaron Logan
A treatment strategy that increases the production of regulatory T cells (Tregs) can prevent graft-versus-host disease (GVHD) in mice, according to research published in The Journal of Experimental Medicine.
One way to prevent GVHD after allogeneic hematopoietic stem cell transplant (allo-HSCT) is to co-transplant large numbers of Tregs, which can suppress the donor cells’ effects on healthy tissue without affecting their ability to kill tumor cells.
This approach is challenging, however, because the Tregs must first be isolated from the donor’s peripheral blood or bone marrow and then cultivated in the lab to produce sufficient numbers for transplant.
Andreas Beilhack, MD, of University Hospital Würzburg in Germany, and his colleagues have found a way to overcome this obstacle, at least in mice.
The team developed a protein agonist called STAR2, which selectively activates TNFR2. The researchers noted that TNF and its receptors, TNFR1 and TNFR2, have been shown to play a crucial role in both GVHD and the graft-versus-leukemia effect.
With their experiments, Dr Beilhack and his colleagues showed that STAR2 binds to TNFR2, activating a signaling pathway that increases the number of natural Tregs in vitro and in vivo.
The team also tested STAR2 in mice with lymphoma. Pretreating the mice with STAR2 protected them from developing GVHD after allo-HSCT. And the donor-derived cells retained their ability to kill lymphoma cells.
In addition, the researchers found that a slightly modified version of STAR2 has a similar effect on human Tregs, which suggests this approach could also prevent GVHD in humans undergoing allo-HSCT.
“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,” Dr Beilhack said.