Clinical and immunologic responses to very low-dose vaccination with WT1 peptide (5 microg/body) in a patient with chronic myelomonocytic leukemia.
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.
Kawakami
Manabu
M
Department of Medicine, National Hospital Organization, Osaka Minami Medical Center, Osaka, Japan.
Oka
Yoshihiro
Y
Tsuboi
Akihiro
A
Harada
Yukie
Y
Elisseeva
Olga A
OA
Furukawa
Yoshio
Y
Tsukaguchi
Machiko
M
Shirakata
Toshiaki
T
Nishida
Sumiyuki
S
Nakajima
Hiroko
H
Morita
Satoshi
S
Sakamoto
Junichi
J
Kawase
Ichiro
I
Oji
Yusuke
Y
Sugiyama
Haruo
H
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*
D019496:Cancer Vaccines; D025721:WT1 Proteins