Development of a novel T-cell immunotherapy targeting HEATR1.

149Background: Allogeneic hematopoietic stem cell transplantation (HCT) often cures acute leukemia. However leukemic relapse remains a major cause of HCT failure, and patients with post-HCT relapse have a very poor prognosis. We are developing T cell immunotherapies targeting leukemia-associated minor histocompatibility (H) antigens to manage post-HCT relapse. Because the presentation of minor H antigens is HLA-restricted, a panel of hematopoietic-restricted, leukemia-associated minor H antigens is required to enable the development of broadly applicable minor H antigen targeted immunotherapy. We previously discovered a HLA- B*0801-restricted, leukemia-associated minor H antigen, HEATR1. We showed that HEATR1-specific T cells can specifically kill leukemic blasts and prevent engraftment in a murine model, implying that this minor H antigen is expressed in leukemic stem cells. We have now developed immunotherapy targeting HEATR1 using genetically modified T cells. Methods: We isolated a HEATR1-specific T c...