title: Chronic myeloid leukemia as an immunological target.
abstract: Various clinical observations have implicated T cells in the control of chronic myeloid leukemia (CML). These observations have in recent years been supported by laboratory results indicating the presence of CML-specific T cells in the lymphocyte repertoire of both normal healthy individuals and disease-bearing patients. Both MHC-unrestricted and MHC-restricted immune effector mechanisms are involved. Donor lymphocyte infusion has produced encouraging GvL effects. However, future adoptive immunotherapy may depend on the isolation and generation of leukemia-specific T cells. Although many proteins may potentially act as leukemia antigens in CML for MHC-restricted cytotoxicity, the bcr-abl fusion protein has been most extensively investigated. There is now much evidence to suggest that the bcr-abl junctional peptides are capable of eliciting both CD4 and CD8 responses in normal healthy donors and CML patients. Furthermore, the T-cell lines generated react with autologous or HLA-matched fresh CML cells, suggesting that the bcr-abl fusion protein can be processed in vivo so that the joining segment is bound to HLA molecules in a configuration and concentration similar to those of the immunizing peptide for antigen recognition by the antigen-specific T-cell receptor. These results also indicate that the bcr-abl junctional peptides may be used for immunotherapy of CML. Other strategies available for immunotherapy of CML include immunologically or genetically manipulated donor T-cell infusion, the use of cytokines, adoptive immunotherapy with leukemia-reactive T-cells expanded ex vivo, and immune gene therapy. Novel and rational immunotherapy may therefore play an important adjuvant role in future in the management of patients with CML.
authors.affiliation: Department of Haematology, University of Wales College of Medicine, Cardiff, UK.
authors.forename: S H
authors.initials: SH
authors.lastname: Lim
authors.forename: S
authors.initials: S
authors.lastname: Coleman
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D016044:Fusion Proteins, bcr-abl / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D007167:Immunotherapy; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000276:immunology* / Q000628:therapy; D008285:Major Histocompatibility Complex; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D016044:Fusion Proteins, bcr-abl