Molecular Horizons - Chloe Sligar, PhD Exit Seminar

Donor blood stem cell transplantation (SCT) is a procedure used to treat various blood malignancies and disorders, including leukaemia. In donor blood SCT, blood stem cells from a healthy donor (graft) are transplanted into a cancer patient (host) who has undergone chemo and/or radio therapy, to generate a new immune system and remove any remaining cancer cells through a mechanism called graft-versus-leukaemia (GVL) immunity. However, a common complication of donor blood SCT is the development of graft-versus-host disease (GVHD), where T cells in the graft recognise the healthy tissues of the host as ‘foreign’ and mount an inflammatory immune response against them, causing severe damage to multiple organs. One therapeutic strategy to prevent GVHD is the use of post-transplant cyclophosphamide (PTCy). While PTCy reduces GVHD severity, the precise mechanism through which this occurs is not fully understood and GVHD still develops. This presentation will focus on the use of PTCy combined with other immunomodulatory therapies, such as interleukin-6 receptor blockade, to prevent GVHD while retaining GVL immunity using humanised mouse models and in vitro proliferation assays.