New potential treatment for graft-versus-host-disease and other inflammatory disorders
Dual cytokine blockers cut toxic reactions after allogeneic stem cell transplantation
A new study led by UC Davis Health researchers showed that blocking IL-6 and TNF cytokines provides a more effective approach to preventing life-threatening graft-versus-host-disease (GVHD), an inflammatory condition that develops in patients after their allogeneic hematopoietic stem cell transplantation (allo-HSCT). The study was published today inBlood.
Allo-HSCT, a treatment for some blood disorders and cancers, entails infusing a donor’s bone marrow stem cells into patients undergoing intensive chemo and radiation therapy. The donated immune cells in the transplanted tissue (graft) initiate an immune response to the patient's tumor cells, leading to favorable graft-versus-tumor (GVT) effects. However, these cells may also attack the patient’s healthy tissues, resulting in potentially lethal graft-versus-host-disease.
What is graft-versus-host-disease?
GVHD is a significant cause of morbidity among allo-HSCT patients. It occurs when donor immune cells in the graft attack multiple organs and induce a “cytokine storm”, an inflated proinflammatory reaction caused by cytokines. Acute GVHD develops suddenly and shortly after transplantation. Chronic GVHD shows up later with delayed inflammation and may lead to tissue fibrosis.
“GVHD remains a major barrier limiting the success of the stem cell transplantation for cancer patients,” said Vice Chair of Research and Distinguished Professor at the Departments of Dermatology and Internal Medicine William Murphy, the senior author on the study.
From single to dual cytokine blockade
TNF and IL-6 are two cytokines that play a key role in many health conditions, including autoimmunity and excessive immune reactions to viruses, such as SARS-CoV-2, the virus causing COVID-19. Current therapies focus on blocking one of these cytokines to control the cytokine storm.
Targeting a single cytokine has been successfully used in certain cases, such as blocking TNF for autoimmunity conditions and IL6 for cytokine release syndrome after CAR T-cell immunotherapy and COVID-19 infections. However, simultaneously blocking both these cytokines has not been evaluated - until now.
Ref:https://health.ucdavis.edu/newsroom/news/headlines/new-potential-treatment-for-graft-versus-host-disease-and-other-inflammatory-disorders/2021/12
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