Figure 1. HLA-A2-mismatched donor-recipient pairs can be used to bypass MHC-restricted fratricide and TCR-mediated hematopoietic stem cell toxicity. In the setting of allogeneic hematopoietic stem cell transplantation (HSCT), two kinds of healthy individuals can be selected to serve as HLA-A*02:01-mismatched donors. Unrelated donors who are HLA-A*02:01-negative but otherwise patient-matched can be used for HSCT and their peripheral blood lymphocytes (PBLs) can be subsequently modified with the HMMR-specific TCR for use in donor lymphocyte infusions (DLIs). Alternatively, HLA-haplotype-mismatched family members who are HLA-A*02:01-negative can be selected for use in HLA-A*02:01-positive acute myeloid leukemia (AML) patients. This therapy could provide three advantages for the patient: (1) a relatively rapid development of donor chimerism through the elimination of residual HSCs; (2) the elimination of leukemic stem cells (LSCs); and (3) the avoidance of graft-vs.-host disease (GvHD) in the presence of potent antitumor responses, through the use of low numbers of adoptively transferred cells expressing a high-avidity HMMR-specific TCR.