“STAR2-Treg” – New strategy to limit side effects of stem cell transplants

Our lab has developed a new approach that may prevent leukemia and lymphoma patients from developing graft-versus-host disease (GvHD) after therapeutic bone marrow transplants. Acute GvHD can be a life-threatening immune reaction following transplantation. We describe the successful application of our strategy in mice in a recent paper “Exogenous TNFR2 activation protects from acute GvHD via host regulatory T cell expansion” that now is being published in The Journal of Experimental Medicine.

Journal of Experimental Medicine STAR2 Tregs FoxP3 Treg therapy regulatory T cells prevent inflammation Beilhack lab Würzburg

“STAR2-Treg”: Fluorescence microscopy of mouse lymph nodes reveals that treatment with STAR2 (right) increases the number of regulatory T cells (Tregs), which express a nuclear protein called FoxP3 (red color). Chopra M et al., J Exp Med 2016

Bone marrow transplants can cure types of
 leukemia and lymphoma because 
immune cells from the
 donor’s bone marrow transplant are capable of killing the patient’s 
cancer cells. 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 (Treg), immune 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 Treg 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. Our “STAR2-Treg”-approach has been published as an article by Martin Chopra et al. in The Journal of Experimental Medicine.


The reseach team under the guidance of Andreas Beilhack and Harald Wajant of Würzburg University Hospital 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 Treg 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 Treg cells. We also found that a slightly modified version of STAR2 has a similar effect on human Treg cells, suggesting that the approach could also prevent GvHD in leukemia and lymphoma patients after bone marrow or hematopoietic stem cell transplants. Our 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.

This work has been truly an interdisciplinary approach including several research teams to advance this novel strategy. As bold our strategy had been, the project required a series of detailed and meticulously conducted experiments covering the fields of medicine, molecular biology, structural biology, immunology, imaging, microbiology, pathology, virology and blood & marrow transplantation. Clearly, substantial resources were required for completion of this project. The financial support came from several generous funding institutions: the Interdisciplinary Center for Clinical Research (IZKF) Würzburg, the Deutsche José Carreras Leukämie-Stiftung, the German Research Council (Deutsche Forschungsgemeinschaft, DFG), the Else-Kröner-Fresenius-Stiftung with additional funding from the Universities of Würzburg and Mainz.



Chopra M, Biehl M, Steinfatt T, Brandl A, Kums J, Amich J, Vaeth M, Kuen J, Holtappels R, Podlech J, Mottok A, Kraus S, Jordán Garrote AL, Bäuerlein CA, Brede C, Ribecchini E, Fick A, Seher A, Polz J, Ottmüller K, Baker J, Nishikii H, Ritz M, Mattenheimer K, Schwinn S, Winter T, Schäfer V, Krappmann S, Einsele H, Mueller TD, Reddehase MJ, Lutz MB, Männel DN, Berberich-Siebelt F, Wajant H*, Beilhack A*. (2016). Exogenous TNFR2 activation protects from acute GvHD by induction of host Treg expansion. J Exp Med, 213:18811900.