title: Clinical and immunologic responses to very low-dose vaccination with WT1 peptide (5 microg/body) in a patient with chronic myelomonocytic leukemia.
abstract: The wild-type Wilms tumor gene, WT1, is overexpressed in myelodysplastic syndrome (MDS) as well as acute myeloid leukemia. In a phase I clinical trial of biweekly vaccination with HLA-A*2402-restricted WT1 peptide for these malignancies, 2 patients with MDS developed severe leukocytopenia in association with a reduction in leukemic blast cells and levels of WT1 messenger RNA (mRNA) after only a single vaccination with 0.3 mg of WT1 peptide. These results indicated that the WT1-specific cytotoxic T-lymphocytes (CTLs) elicited by WT1 vaccination eradicated the WT1-expressing transformed stem or progenitor cells and that MDS patients with little normal hematopoiesis required a new strategy of WT1 vaccination to avoid severe leukocytopenia. We describe the first trial for a 57-year-old male patient with chronic myelomonocytic leukemia who was vaccinated biweekly with a small quantity (5 microg/body) of WT1 peptide. After the start of vaccination, the leukocyte and monocyte counts (13,780/microL and 1930/microL, respectively) gradually decreased to within the normal range in association with a reduction in the WT1 mRNA level. Simultaneously, the percentage of WT1-specific CTLs as measured by the HLA-WT1 tetramer assay increased. This case demonstrates for the first time that vaccination with as little as 5 microg of WT1 peptide can induce WT1-specific immune responses and resultant clinical responses.
authors.affiliation: Department of Medicine, National Hospital Organization, Osaka Minami Medical Center, Osaka, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Kawakami
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Oka
authors.forename: Akihiro
authors.initials: A
authors.lastname: Tsuboi
authors.forename: Yukie
authors.initials: Y
authors.lastname: Harada
authors.forename: Olga A
authors.initials: OA
authors.lastname: Elisseeva
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Furukawa
authors.forename: Machiko
authors.initials: M
authors.lastname: Tsukaguchi
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Shirakata
authors.forename: Sumiyuki
authors.initials: S
authors.lastname: Nishida
authors.forename: Hiroko
authors.initials: H
authors.lastname: Nakajima
authors.forename: Satoshi
authors.initials: S
authors.lastname: Morita
authors.forename: Junichi
authors.initials: J
authors.lastname: Sakamoto
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kawase
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Oji
authors.forename: Haruo
authors.initials: H
authors.lastname: Sugiyama
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D002454:Cell Differentiation; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D015477:Leukemia, Myelomonocytic, Chronic / Q000188:drug therapy* / Q000276:immunology; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D025721:WT1 Proteins / Q000008:administration & dosage* / Q000276:immunology*
chemical_list: D019496:Cancer Vaccines; D025721:WT1 Proteins