ODC-deficient T cells

ODC-deficient T cells are a type of donor T cell engineered with a specific deficiency in ornithine decarboxylase (ODC), a key enzyme involved in polyamine synthesis. This cellular therapy is being investigated in the context of allogeneic hematopoietic cell transplantation (Allo-HCT) to mitigate graft-versus-host disease (GVHD) while preserving the beneficial graft-versus-leukemia/lymphoma (GVL) effect. The mechanism involves altered polyamine metabolism, which leads to enhanced PD-L1/PD-1 mediated inhibition of T cell receptor (TCR) signaling, disruption of the PI3-AKT-mTOR pathway, augmented mitochondrial reactive oxygen species production and dysfunction, reduced T cell proliferation, increased T cell exhaustion, and a decreased differentiation of stem-like memory T cells into tissue-resident effector memory T cells. These effects collectively contribute to the attenuation of GVHD.