Donor lymphocytes engineered with SA-FasL to avoid aGVHD

Shrestha P, Turan A, Batra L, et al. Engineering Donor Lymphocytes with Fas Ligand Protein Effectively Prevents Acute Graft-Versus-Host Disease. Blood Advances. 2023; (doi: 10.1182/bloodadvances.2022008495).

The key to avoiding acute graft-versus-host disease (aGVHD) after hematopoietic stem cell transplantation is in the design of the donor T cells, researchers report. If engineered to express a certain type of Fas ligand (FasL) protein directly on the cell surface, donor cells effectively eliminate alloreactive T effector cells (Teffs) — which are strongly implicated in the development of post-transplant aGVHD. In experiments, T cells with surface expression of FasL plus streptavidin (SA-FasL) were transplanted in lethally irradiated haploidentical mice following cotransplantation with bone marrow cells. For comparison, control subjects were transplanted with nonengineered splenocytes. While 100% of the control mice developed aGVHD, the condition was prevented in >70% of mice receiving SA-FasL splenocytes. The technique also headed off aGVHD in NSG mice that were transplanted with SA-FasL-engineered human peripheral blood mononuclear cells. Once the cells are activated, they surrender to apoptosis in response to host alloantigens both in vitro and in vivo, the researchers write. Thus, engineering SA-FasL protein an donor cells may represent an approach with potential for prevention of aGVHD.

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Tags: GVHD, hematopoietic, Acute GVHD, aGVHD, T cells, hematopoietic transplantation, T cell, hematopoietic cell transplantation

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