CHRONIC MYELOID-LEUKEMIA AS AN IMMUNOLOGICAL TARGET

Various clinical observations have implicated T cells in the control o f chronic myeloid leukemia (CML). These observations have in recent ye ars been supported by laboratory results indicating the presence of CM L-specific T cells in the lymphocyte repertoire of both normal healthy individuals and disease-bearing patients. Both MHC-unrestricted and M HC-restricted immune effector mechanisms are involved. Donor lymphocyt e infusion has produced encouraging GvL effects. However, future adopt ive immunotherapy may depend on the isolation and generation of leukem ia-specific T cells. Although many proteins may potentially act as leu kemia antigens in CML for MHC-restricted cytotoxicity, the bcr-abl fus ion protein has been most extensively investigated. There is now much evidence to suggest that the bcr-abl junctional peptides are capable o f eliciting both CD4 and CD8 responses in normal healthy donors and CM L patients. Furthermore, the T-cell lines generated react with autolog ous 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 thos e of the immunizing peptide for antigen recognition by the antigen-spe cific T-cell receptor. These results also indicate that the bcr-abl ju nctional peptides may be used for immunotherapy of CML. Other strategi es available for immunotherapy of CML include immunologically or genet ically manipulated donor T-cell infusion, the use of cytokines, adopti ve immunotherapy with leukemia-reactive T-cells expanded ex vivo, and immune gene therapy. Novel and rational immunotherapy may therefore pl ay an important adjuvant role in future in the management of patients with CML. (C) 1997 Wiley-Liss, Inc.