| Stem cell transplantation and high-dose chemotherapy is the most effective treatment for certain cancers such as leukemia and lymphoma. It is reported from the leukemia and lymphoma society that there are about 28,540 new cases of leukemia and 54,370 cases of non-Hodgkin lymphoma are diagnosed each year in the United States. Allogeneic stem cell transplantation has been widely studied due to the lack of HLA (Human Leukocyte Antigen)-matched donors. However, the application of allogeneic stem cell transplantation is restricted by the development of severe graft-versus-host disease (GvHD), which is believed to be caused by donor T cells. Depletion of donor T cells abrogates GvHD, while the chance of viral infection and leukemia relapse is increased due to the delay of immuno-reconstitution after extensive T cell depletion. Selective depletion of alloreactive T cells which mediate GvHD from donors, while retaining T cells with reactivity to pathogens and third party antigens is an alternative strategy that may protect the patient from opportunistic infections and shorten the immunodeficiency post transplantation. However, the success of this strategy depends on the extent of alloreactive T cell depletion and remaining anti-viral and third party reactivity. One of the main challenges associated with inefficient alloreactive T cell depletion is the stimulation and detection of potential alloreactive T cells.; This study is focusing optimizing the condition for generating alloreactive T cells in vitro; selection of the optimum combination of activation antigens to define alloreactive T cells; and applying immunomagnetic cell separation method to maximize depletion of alloreactivity with the preservation of anti-third-party reactivity for clinical application. |
