Targeting alloreactive donor T-cells to hematopoietic system-restricted minor histocompatibility antigens to dissect graft-versus-leukemia effects from graft-versus-host disease after allogeneic stem cell transplantation.
The graft-versus-leukemia (GVL) effect of HLA-identical allogeneic stem cell transplantation is mainly mediated by alloreactive T-cells directed at the minor histocompatibility antigens (H ags) expressed on the leukemic cells of the recipient. Minor H ags are major histocompatibility complex-bound polymorphic peptides that are derived from intracellular proteins and that can show ubiquitous or hematopoietic system-restricted expression. Whereas ubiquitous minor H ags are involved both in the GVL effect and in graft-versus-host disease (GVHD), hematopoietic system-specific minor H ags expressed on leukemic cells are considered important targets for leukemia-specific cellular immunotherapy with a low risk of GVHD. This review will summarize the current knowledge of the immunobiology of minor H ags and discuss the advantages and drawbacks of cellular immunotherapy strategies that aim to separate the GVL effect from GVHD by targeting donor T-cells to hematopoietic system-specific minor H ags.
Mutis
Tuna
T
Department of Hematology, University Medical Center Utrecht, Utrecht, The Netherlands. t.mutis@azu.nl
D000818:Animals; D006086:Graft vs Host Disease / Q000276:immunology; D020544:Graft vs Leukemia Effect / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation; D006413:Hematopoietic System / Q000166:cytology / Q000276:immunology; D006801:Humans; D017710:Lymphocyte Transfusion / Q000379:methods*; D015778:Minor Histocompatibility Antigens; D014181:Transplantation Immunology
D015778:Minor Histocompatibility Antigens