EBMT 2022 | Engineered T-cells to prevent GvHD in leukemia

Feiyan Mo, Baylor College of Medicine, Houston, TX, describes the rationale and results of a pre-clinical study aiming to suppress graft-versus-host disease (GvHD) through T-cell engineering. Based on previous experiments showing that OX40 is upregulated on activated CD4+ T-cells in GvHD animal models and patients, and that monoclonal antibodies blocking the OX40 signaling pathway can mitigate GvHD without impairing anti-tumor immunity, T-cells were engineered to express OX40-specific chimeric receptors enabling them to recognize and eliminate OX40-expressing activated alloreactive T-cells. In vivo experiments in mouse models showed that these engineered T-cells effectively suppressed GvHD. These engineered T-cells were then combined with CD19-directed CAR-Ts, resulting in a single engineered T-cell product that can simultaneously protect against GvHD and leukemia relapse post-transplantation. Because of concerns about inflammatory responses caused by this T-cell platform and its effects on other beneficial T-cell subsets expressing OX40, regulatory T-cells are currently being developed to express OX40, which will help suppress alloreactivity without causing additional inflammation. In addition, this T-cell platform is going to be evaluated in a non-human primate GvHD model to evaluate the safety and efficacy of this approach in an animal model that resembles human GvHD pathophysiology more closely. This interview took place at the 48th Annual Meeting of the European Group for Blood and Marrow Transplantation (EBMT) 2022, which was held virtually.