ex vivo-generated T cell precursors

Ex vivo-generated T cell precursors (PreTs) are a cellular therapy developed to address delayed immune reconstitution following allogeneic hematopoietic cell transplant (allo-HCT), a condition that increases the risk of infection, graft failure, and relapse. These PreTs are generated from hematopoietic stem and progenitor cells (HSPCs) using an immobilized DLL4-Fc (recombinant Delta-like 4 fused to an Fc domain) platform, which is scalable and GMP-compatible. Upon adoptive transfer, PreTs successfully engraft in the thymus, significantly increasing total thymic cellularity and promoting the regeneration of the thymic microenvironment, including thymic epithelial cells (TECs) and endothelial cells (ECs). They enhance *de novo* thymopoiesis from donor LSK cells, leading to increased numbers of mature CD4+ and CD8+ single-positive T cells in both the thymus and spleen. PreT therapy has demonstrated effectiveness in preclinical models, even under conditions of heightened thymic impairment due to aging or post-transplant cyclophosphamide, by enhancing peripheral T cell function, antiviral responses, and antitumor activity without inducing graft-versus-host disease. The cultured PreTs express higher levels of thymotropic factors such as *Tnfα1*, *Fgf7*, *Bmp4*, and *Lta*, which support stromal regeneration.

Other names

PreT