04 January 2022

Researchers have found that giving a combination of cytokine blockers soon after a stem cell transplant reduces the risk of graft-versus-host-disease (GVHD) in mice.

During acute GVHD, small proteins called cytokines are produced, including tumour necrosis factor (TNF) and interleukin-6 (IL-6).

“Allogeneic haematopoietic stem cell transplantation remains a potential curative option for treating a variety of haematologic diseases, but acute and chronic GVHD remain major barriers limiting efficacy,” wrote Professor William Murphy of the University of California, Davis, CA, USA, and colleagues in the journal Blood.

Given the overlapping effects of TNF and IL-6, Professor Murphy and his team investigated using mouse models whether the combined blockade of both TNF and IL-6R leads to greater protection from GVHD.

“Early administration of combined blockade resulted in greater protection and survival from acute gut GVHD compared with single blockade regimens and even development of later chronic skin GVHD,” they report.

“Importantly, double cytokine blockade preserved graft-versus-tumour effects,” they add.

Professor Murphy comments: “GVHD remains a major barrier limiting the success of the stem cell transplantation for cancer patients.

“Surprisingly, only a single cytokine blockade to IL6 or TNF has been evaluated in preventing GVHD, which gave disappointing clinical results. Given the important and possibly redundant roles these powerful inflammatory cytokines play, it made sense that combination approaches would be needed for greater efficacy.”

“The increased efficacy of combined blockade suggests that this approach to treating diseases caused by inflammation may have greater benefit in other clinical settings,” he concludes.


Khuat LT, Vick LV, Dunai C, Collins CP, More SK, Le CT, Pai CS, Stoffel KM, Maverakis E, Canter RJ, Monjazeb AM, Longo DL, Abedi M, Choi E, Blazar BR, Dave M, Murphy WJ. (2021) “Increased efficacy of dual pro-inflammatory cytokine blockade on acute GVHD while maintaining GVT effects.” Blood, doi: 10.1182/blood.2021011216


Link: https://ashpublications.org/blood/article-abstract/138/24/2583/476651/Increased-efficacy-of-dual-proinflammatory   

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