T cell optimization for graft-versus-leukemia responses

Protection from relapse after allogeneic hematopoietic cell transplantation (HCT) is partly due to donor T cell-mediated graft-versus-leukemia (GVL) immune responses. Relapse remains common in HCT recipients, but strategies to augment GVL could significantly improve outcomes after HCT. Donor T cells with alpha beta T cell receptors (TCRs) mediate GVL through recognition of minor histocompatibility antigens and alloantigens in HLA-matched and -mismatched HCT, respectively. T cells specific for other leukemia-associated antigens, including nonpolymorphic antigens and neoantigens, may also deliver an antileukemic effect. gamma delta T cells may contribute to GVL, although their biology and specificity are less well understood. Vaccination or adoptive transfer of donor derived T cells with natural or transgenic receptors are strategies with potential to selectively enhance alpha beta and gamma delta T cell GVL effects.