Wilms tumor gene peptide-based immunotherapy for patients with overt leukemia from myelodysplastic syndrome (MDS) or MDS with myelofibrosis.
The Wilms tumor gene, WT1, is overexpressed not only in leukemias and myelodysplastic syndrome (MDS) but also in various types of solid tumors, including lung and breast cancer, and the WT1 protein is a tumor antigen for these malignancies. In clinical trials of WT1 peptide-based cancer immunotherapy, patients with overt leukemia from MDS or MDS with myelofibrosis were injected intradermally with 0.3 mg of an HLA-A*2402-restricted, 9-mer WT1 peptide emulsified with Montanide ISA51 adjuvant. Only a single dose of WT1 vaccination resulted in an increase in WT1-specific cytotoxic T-lymphocytes, which was followed by a rapid reduction in leukemic blast cells. Severe leukopenia and local erythema at the injection sites of WT1 peptide were observed as adverse effects. These results have provided us with the first clinical evidence suggesting that WT1 peptide-based immunotherapy is an attractive treatment for patients with leukemias or MDS.
Oka
Yoshihiro
Y
Department of Molecular Medicine, Osaka University Medical School, Suita City, Osaka, Japan.
Tsuboi
Akihiro
A
Murakami
Masaki
M
Hirai
Manabu
M
Tominaga
Nobuhiko
N
Nakajima
Hiroko
H
Elisseeva
Olga A
OA
Masuda
Tomoki
T
Nakano
Akiko
A
Kawakami
Manabu
M
Oji
Yusuke
Y
Ikegame
Kazuhiro
K
Hosen
Naoki
N
Udaka
Keiko
K
Yasukawa
Masaki
M
Ogawa
Hiroyasu
H
Kawase
Ichiro
I
Sugiyama
Haruo
H
D000368:Aged; D000951:Antigens, Neoplasm / Q000008:administration & dosage* / Q000627:therapeutic use; D005260:Female; D015234:HLA-A Antigens / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007938:Leukemia / Q000209:etiology / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000473:pathology*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use; D055728:Primary Myelofibrosis / Q000473:pathology; D016896:Treatment Outcome; D014611:Vaccination; D025721:WT1 Proteins / Q000276:immunology*
D000951:Antigens, Neoplasm; D015234:HLA-A Antigens; D010446:Peptide Fragments; D025721:WT1 Proteins