Immunotherapeutic strategies in chronic myeloid leukemia.
Several clinical observations demonstrate that immunologic effects are important in chronic myeloid leukemia (CML). The characteristic BCR-ABL fusion protein is a leukemia-specific antigen, and it has therefore received much immunologic attention, especially regarding the amino acid sequences that span the e14a2 junction. Other attractive targets are the Wilms' tumor 1 antigen and the PR1 epitope from proteinase 3, a granule protein overexpressed in CML. Imatinib may modulate several components of the immune response, although the clinical relevance of this effect is uncertain. In clinical trials, peptide vaccination appears safe and undoubtedly produces clinical effects, but randomized trials are now required to see if these are distinct from the effects of other concurrent therapy. These trials will be difficult to orchestrate in the competitive environment of novel therapies for CML.
Clark
Richard E
RE
Department of Haematology, Royal Liverpool University Hospital, Prescot St., Liverpool L7 8XP, UK. clarkre@liverpool.ac.uk
D000951:Antigens, Neoplasm / Q000737:chemistry / Q000276:immunology*; D001549:Benzamides; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D017635:Clonal Anergy; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D016044:Fusion Proteins, bcr-abl / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D006801:Humans; D000068877:Imatinib Mesylate; D007167:Immunotherapy / Q000379:methods*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D053146:Myeloblastin / Q000737:chemistry / Q000276:immunology; D009363:Neoplasm Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D011743:Pyrimidines / Q000494:pharmacology / Q000627:therapeutic use; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014611:Vaccination; D022223:Vaccines, Subunit / Q000276:immunology / Q000627:therapeutic use; D025721:WT1 Proteins / Q000737:chemistry / Q000276:immunology
D000951:Antigens, Neoplasm; D001549:Benzamides; D019496:Cancer Vaccines; D000939:Epitopes; D009363:Neoplasm Proteins; D010446:Peptide Fragments; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D022223:Vaccines, Subunit; D025721:WT1 Proteins; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl; D053146:Myeloblastin