Jarrod Dudakov, PhD

One promising candidate therapy for improving T cell reconstitution following hematopoietic stem cell transplantation (HSCT) is the adoptive transfer of in vitro generated precursor-T cells, which aids short-term T cell regeneration but, intriguingly, also improves long-term thymic function — well beyond the expected lifespan of the transplanted pre-T cells. This suggests that the transferred pre-T cells themselves play a role in mediating long-term enhanced thymic function. We are currently characterizing regeneration of the thymic stromal microenvironment and seeking to reveal the pre-T derived signals mediating prolonged regeneration. We are also attempting to manipulate recently identified pathways governing the importation of blood-borne T cell progenitors to allow enhanced seeding of the thymus by in vitro generated pre-T cells. Successfully achieving this will not only enhance regeneration following HSCT, but will also lay the foundation for the use of “off the shelf” pre-T cells for the development of, among other things, tumour-specific T cells as well as the induction of tolerance to solid organ transplants — both of which are a significant unmet clinical need.