title: Characterizing and optimizing immune responses to leukaemia antigens after allogeneic stem cell transplantation.
abstract: Allogeneic stem cell transplantation remains a curative treatment for haematological malignancies resistant to other treatment approaches through the unique graft-versus-leukaemia effect (GvL). However, the lack of specificity of this response results in the targeting of normal tissue, and the morbidity and mortality associated with graft-versus-host disease (GvHD). Further improvements in exploiting the GvL effect to prevent relapse in high-risk leukaemias while minimizing toxicity have focused on the use of targeted anti-leukaemic immunotherapy. These strategies include the use of vaccines against minor histocompatibility antigens (HA-1, HA-2 and H-Y) and leukaemia-specific antigens (proteinase 3, Wilms' tumour 1 and BCR-ABL), and the adoptive transfer of leukaemia-specific T cells. The unique post-transplant milieu, which is characterized by lymphopenia, regulatory T-cell depletion and the release of growth factors, offers the opportunity to promote the expansion of engrafted T cells and enhance the specific GvL response. Techniques to reduce regulatory T-cell control over T-cell responses to leukaemia antigens could further enhance GvL reactivity. Finally, these approaches to increase GvL effects would be facilitated by transplant approaches to deplete GvHD alloresponses selectively while preserving GvL reactivity.
authors.affiliation: Department of Haematology, 4th Floor Commonwealth Building, Hammersmith Hospital, DuCane Road, London W12 0NN, UK. k.rezvani@imperial.ac.uk
authors.forename: Katayoun
authors.initials: K
authors.lastname: Rezvani
authors.forename: A John
authors.initials: AJ
authors.lastname: Barrett
mesh_terms: D000951:Antigens, Neoplasm / Q000276:immunology / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy; D016044:Fusion Proteins, bcr-abl / Q000276:immunology; D020544:Graft vs Leukemia Effect / Q000276:immunology*; D006801:Humans; D007109:Immunity; D007938:Leukemia / Q000276:immunology* / Q000601:surgery; D008213:Lymphocyte Activation; D015778:Minor Histocompatibility Antigens / Q000276:immunology; D012697:Serine Endopeptidases / Q000276:immunology; D033581:Stem Cell Transplantation; D013601:T-Lymphocytes / Q000276:immunology; D014184:Transplantation, Homologous; D025721:WT1 Proteins / Q000276:immunology
chemical_list: D000951:Antigens, Neoplasm; D015778:Minor Histocompatibility Antigens; D025721:WT1 Proteins; D016044:Fusion Proteins, bcr-abl; D012697:Serine Endopeptidases
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